B-Lymphocyte Subsets: A classification of B-lymphocytes based on structurally or functionally different populations of cells.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Germinal Center: The activated center of a lymphoid follicle in secondary lymphoid tissue where B-LYMPHOCYTES are stimulated by antigens and helper T cells (T-LYMPHOCYTES, HELPER-INDUCER) are stimulated to generate memory cells.Immunoglobulin M: A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.Immunoglobulin D: An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B LYMPHOCYTES.Spleen: An encapsulated lymphatic organ through which venous blood filters.Antigens, CD19: Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.Mice, Inbred C57BLImmunoglobulin Heavy Chains: The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.B-Cell Activating Factor: A tumor necrosis factor superfamily member that plays a role in the regulation of B-LYMPHOCYTE survival. It occurs as a membrane-bound protein that is cleaved to release an biologically active soluble form with specificity to TRANSMEMBRANE ACTIVATOR AND CAML INTERACTOR PROTEIN; B-CELL ACTIVATION FACTOR RECEPTOR; and B-CELL MATURATION ANTIGEN.Lymphocyte Cooperation: T-cell enhancement of the B-cell response to thymic-dependent antigens.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Antigens, CD40: A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Precursor Cells, B-Lymphoid: Lymphocyte progenitor cells that are restricted in their differentiation potential to the B lymphocyte lineage. The pro-B cell stage of B lymphocyte development precedes the pre-B cell stage.Gene Rearrangement, B-Lymphocyte: Ordered rearrangement of B-lymphocyte variable gene regions coding for the IMMUNOGLOBULIN CHAINS, thereby contributing to antibody diversity. It occurs during the differentiation of the IMMATURE B-LYMPHOCYTES.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.Immunoglobulins: Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.Antigens, CD5: Glycoproteins expressed on all mature T-cells, thymocytes, and a subset of mature B-cells. Antibodies specific for CD5 can enhance T-cell receptor-mediated T-cell activation. The B-cell-specific molecule CD72 is a natural ligand for CD5. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)Immunologic Memory: The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.Genes, Immunoglobulin: Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).Mice, Inbred BALB CLymphoma, B-Cell: A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.B-Cell Activation Factor Receptor: A member of the tumor necrosis factor receptor superfamily that specifically binds B-CELL ACTIVATING FACTOR. It is found on B-LYMPHOCYTES and plays a role in maturation and survival of B-cells. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Antigens, Differentiation, B-Lymphocyte: Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.Receptors, Complement 3d: Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.Sialic Acid Binding Ig-like Lectin 2: A lectin and cell adhesion molecule found in B-LYMPHOCYTES. It interacts with SIALIC ACIDS and mediates signaling from B-CELL ANTIGEN RECEPTORS.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Immunoglobulin mu-Chains: The class of heavy chains found in IMMUNOGLOBULIN M. They have a molecular weight of approximately 72 kDa and they contain about 57 amino acid residues arranged in five domains and have more oligosaccharide branches and a higher carbohydrate content than the heavy chains of IMMUNOGLOBULIN G.Gene Rearrangement, B-Lymphocyte, Heavy Chain: Ordered rearrangement of B-lymphocyte variable gene regions of the IMMUNOGLOBULIN HEAVY CHAINS, thereby contributing to antibody diversity. It occurs during the first stage of differentiation of the IMMATURE B-LYMPHOCYTES.Antigens, CD27: A member of the tumor necrosis factor receptor superfamily found on most T-LYMPHOCYTES. Activation of the receptor by CD70 ANTIGEN results in the increased proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Epitopes, B-Lymphocyte: Antigenic determinants recognized and bound by the B-cell receptor. Epitopes recognized by the B-cell receptor are located on the surface of the antigen.Antigens, T-Independent: Antigens which may directly stimulate B lymphocytes without the cooperation of T lymphocytes.Receptors, CXCR5: CXCR receptors isolated initially from BURKITT LYMPHOMA cells. CXCR5 receptors are expressed on mature, recirculating B-LYMPHOCYTES and are specific for CHEMOKINE CXCL13.CD40 Ligand: A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.Somatic Hypermutation, Immunoglobulin: A programmed mutation process whereby changes are introduced to the nucleotide sequence of immunoglobulin gene DNA during development.Gene Rearrangement, B-Lymphocyte, Light Chain: Ordered rearrangement of B-lymphocyte variable gene regions coding for the kappa or lambda IMMUNOGLOBULIN LIGHT CHAINS, thereby contributing to antibody diversity. It occurs during the second stage of differentiation of the IMMATURE B-LYMPHOCYTES.Antigens, CD79: A component of the B-cell antigen receptor that is involved in B-cell antigen receptor heavy chain transport to the PLASMA MEMBRANE. It is expressed almost exclusively in B-LYMPHOCYTES and serves as a useful marker for B-cell NEOPLASMS.Immunoglobulin kappa-Chains: One of the types of light chains of the immunoglobulins with a molecular weight of approximately 22 kDa.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.Antibodies, Anti-Idiotypic: Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Immunophenotyping: Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.Antibody-Producing Cells: Cells of the lymphoid series that can react with antigen to produce specific cell products called antibodies. Various cell subpopulations, often B-lymphocytes, can be defined, based on the different classes of immunoglobulins that they synthesize.Lymphoid Tissue: Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.Herpesvirus 4, Human: The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.Interleukin-4: A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.Dendritic Cells, Follicular: Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional DENDRITIC CELLS associated with T-CELLS. They are derived from MESENCHYMAL STEM CELLS and are negative for class II MHC antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have FC RECEPTORS and C3B RECEPTORS that hold antigen in the form of ANTIGEN-ANTIBODY COMPLEXES on their surfaces for long periods for recognition by B-CELLS.Clone Cells: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)Immunoglobulin Isotypes: The classes of immunoglobulins found in any species of animal. In man there are nine classes that migrate in five different groups in electrophoresis; they each consist of two light and two heavy protein chains, and each group has distinguishing structural and functional properties.Lymphocyte Count: The number of LYMPHOCYTES per unit volume of BLOOD.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Lymphopoiesis: Formation of LYMPHOCYTES and PLASMA CELLS from the lymphoid stem cells which develop from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW. These lymphoid stem cells differentiate into T-LYMPHOCYTES; B-LYMPHOCYTES; PLASMA CELLS; or NK-cells (KILLER CELLS, NATURAL) depending on the organ or tissues (LYMPHOID TISSUE) to which they migrate.Chemokine CXCL13: A CXC chemokine that is chemotactic for B-LYMPHOCYTES. It has specificity for CXCR5 RECEPTORS.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Immunoglobulin lambda-Chains: One of the types of light chain subunits of the immunoglobulins with a molecular weight of approximately 22 kDa.Leukemia, Lymphocytic, Chronic, B-Cell: A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.Immunoglobulin Light Chains: Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.Lymphopenia: Reduction in the number of lymphocytes.Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.Antigens: Substances that are recognized by the immune system and induce an immune reaction.B-Cell-Specific Activator Protein: A transcription factor that is essential for CELL DIFFERENTIATION of B-LYMPHOCYTES. It functions both as a transcriptional activator and repressor to mediate B-cell commitment.B-Lymphocytes, Regulatory: B-cells that have a role in regulating the immune response including the production of CYTOKINES. This function is in addition to their traditional role in making antibodies.Cell SeparationMembrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Lymph Nodes: They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cytidine Deaminase: An enzyme that catalyzes the deamination of cytidine, forming uridine. EC 3.5.4.5.Antibodies, Antinuclear: Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Immunologic Deficiency Syndromes: Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.Trinitrobenzenes: Benzene derivatives which are substituted with three nitro groups in any position.Tumor Necrosis Factor Ligand Superfamily Member 13: A member of tumor necrosis factor superfamily found on MACROPHAGES; DENDRITIC CELLS and T-LYMPHOCYTES. It occurs as transmembrane protein that can be cleaved to release a secreted form that specifically binds to TRANSMEMBRANE ACTIVATOR AND CAML INTERACTOR PROTEIN; and B CELL MATURATION ANTIGEN.Antigen Presentation: The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)Immunoglobulin A: Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.Mice, Inbred CBABurkitt Lymphoma: A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.Leukemia, B-Cell: A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood.Immunoglobulin Light Chains, Surrogate: An immunolglobulin light chain-like protein composed of an IMMUNOGLOBULIN VARIABLE REGION-like peptide (such as light chain like lambda5 peptide) and an IMMUNOGLOBULIN CONSTANT REGION-like peptide (such as Vpreb1 peptide). Surrogate light chains associate with MU IMMUNOGLOBULIN HEAVY CHAINS in place of a conventional immunoglobulin light chains to form pre-B cell receptors.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Hemolytic Plaque Technique: A method to identify and enumerate cells that are synthesizing ANTIBODIES against ANTIGENS or HAPTENS conjugated to sheep RED BLOOD CELLS. The sheep red blood cells surrounding cells secreting antibody are lysed by added COMPLEMENT producing a clear zone of HEMOLYSIS. (From Illustrated Dictionary of Immunology, 3rd ed)Antibody Diversity: The phenomenon of immense variability characteristic of ANTIBODIES. It enables the IMMUNE SYSTEM to react specifically against the essentially unlimited kinds of ANTIGENS it encounters. Antibody diversity is accounted for by three main theories: (1) the Germ Line Theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the Somatic Mutation Theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the Gene Rearrangement Theory, which holds that antibody diversity is generated by the rearrangement of IMMUNOGLOBULIN VARIABLE REGION gene segments during the differentiation of the ANTIBODY-PRODUCING CELLS.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).Histocompatibility Antigens Class II: Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Receptors, IgE: Specific molecular sites on the surface of B- and T-lymphocytes which combine with IgEs. Two subclasses exist: low affinity receptors (Fc epsilon RII) and high affinity receptors (Fc epsilon RI).Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Models, Immunological: Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.Antibodies, Monoclonal, Murine-Derived: Antibodies obtained from a single clone of cells grown in mice or rats.Phenylacetates: Derivatives of phenylacetic acid. Included under this heading are a variety of acid forms, salts, esters, and amides that contain the benzeneacetic acid structure. Note that this class of compounds should not be confused with derivatives of phenyl acetate, which contain the PHENOL ester of ACETIC ACID.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Transmembrane Activator and CAML Interactor Protein: A tumor necrosis factor receptor superfamily member found expressed on peripheral B-LYMPHOCYTES. It has specificity for B-CELL MATURATION ANTIGEN and TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 13.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Mice, Inbred MRL lpr: A mouse substrain that is genetically predisposed to the development of systemic lupus erythematosus-like syndrome, which has been found to be clinically similar to the human disease. It has been determined that this mouse strain carries a mutation in the fas gene. Also, the MRL/lpr is a useful model to study behavioral and cognitive deficits found in autoimmune diseases and the efficacy of immunosuppressive agents.Immunoglobulin J-Chains: A 15 kD "joining" peptide that forms one of the linkages between monomers of IMMUNOGLOBULIN A or IMMUNOGLOBULIN M in the formation of polymeric immunoglobulins. There is one J chain per one IgA dimer or one IgM pentamer. It is also involved in binding the polymeric immunoglobulins to POLYMERIC IMMUNOGLOBULIN RECEPTOR which is necessary for their transcytosis to the lumen. It is distinguished from the IMMUNOGLOBULIN JOINING REGION which is part of the IMMUNOGLOBULIN VARIABLE REGION of the immunoglobulin light and heavy chains.Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli.Immunoglobulin delta-Chains: The class of heavy chains found in IMMUNOGLOBULIN D. They have a molecular weight of approximately 64 kDa and they contain about 500 amino acid residues arranged in four domains and an oligosaccharide component covalently bound to the Fc fragment constant region.HemocyaninPre-B Cell Receptors: Membrane proteins in precursor B-LYMPHOCYTES (pre-B Cells). They are composed of membrane-bound MU IMMUNOGLOBULIN HEAVY CHAINS in complex with SURROGATE LIGHT CHAINS instead of conventional IMMUNOGLOBULIN LIGHT CHAINS. Only successful rearrangement of the VDJ segments, at the Ig heavy chain gene locus (IMMUNOGLOBULIN HEAVY CHAIN GENES), will generate mu heavy chains that can pair with surrogate light chains. Thus formation of the pre-B cell receptors is an important checkpoint in the development of mature B cells.Toll-Like Receptor 9: A pattern recognition receptor that binds unmethylated CPG CLUSTERS. It mediates cellular responses to bacterial pathogens by distinguishing between self and bacterial DNA.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Immunoglobulin E: An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Antigen-Presenting Cells: A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.Pokeweed Mitogens: Proteins isolated from the roots of the pokeweed, Phytolacca americana, that agglutinate some erythrocytes, stimulate mitosis and antibody synthesis in lymphocytes, and induce activation of plasma cells.Leukemia, Lymphoid: Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.Self Tolerance: The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Clonal Deletion: Removal, via CELL DEATH, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion.Antigens, CD45: High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Peyer's Patches: Lymphoid tissue on the mucosa of the small intestine.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Immunoglobulin gamma-Chains: Heavy chains of IMMUNOGLOBULIN G having a molecular weight of approximately 51 kDa. They contain about 450 amino acid residues arranged in four domains and an oligosaccharide component covalently bound to the Fc fragment constant region. The gamma heavy chain subclasses (for example, gamma 1, gamma 2a, and gamma 2b) of the IMMUNOGLOBULIN G isotype subclasses (IgG1, IgG2A, and IgG2B) resemble each other more closely than the heavy chains of the other IMMUNOGLOBULIN ISOTYPES.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Immunoglobulin Joining Region: A segment of the immunoglobulin heavy chains, encoded by the IMMUNOGLOBULIN HEAVY CHAIN GENES in the J segment where, during the maturation of B-LYMPHOCYTES; the gene segment for the variable region upstream is joined to a constant region gene segment downstream. The exact position of joining of the two gene segments is variable and contributes to ANTIBODY DIVERSITY. It is distinguished from the IMMUNOGLOBULIN J CHAINS; a separate polypeptide that serves as a linkage piece in polymeric IGA or IGM.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Proto-Oncogene Proteins c-bcl-6: A DNA-binding protein that represses GENETIC TRANSCRIPTION of target genes by recruiting HISTONE DEACETYLASES. Aberrant Blc-6 expression is associated with certain types of human B-CELL LYMPHOMA.Cell Lineage: The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.Immunoglobulin Idiotypes: Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Dendritic Cells: Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Hypergammaglobulinemia: An excess of GAMMA-GLOBULINS in the serum due to chronic infections or PARAPROTEINEMIAS.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Epitopes: Sites on an antigen that interact with specific antibodies.NitrophenolsReverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Mice, Inbred AInterleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Antigens, CD38: A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS.Antibody Affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.Common Variable Immunodeficiency: Heterogeneous group of immunodeficiency syndromes characterized by hypogammaglobulinemia of most isotypes, variable B-cell defects, and the presence of recurrent bacterial infections.Mice, SCID: Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.Genes, RAG-1: Genes involved in activating the enzyme VDJ recombinase. RAG-1 is located on chromosome 11 in humans (chromosome 2 in mice) and is expressed exclusively in maturing lymphocytes.Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.Interleukin-10: A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.Immunity, Humoral: Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Thymus Gland: A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.Interleukin-7: A cytokine produced by bone marrow stromal cells that promotes the growth of B-LYMPHOCYTE precursors and is co-mitogenic with INTERLEUKIN-2 for mature T-LYMPHOCYTE activation.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Receptors, Interleukin-21: Cell surface receptors for interleukin 21. They are heterodimeric proteins found on DENDRITIC CELLS and LYMPHOCYTES that consist of the INTERLEUKIN-21 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR COMMON BETA SUBUNIT.Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Receptors, IgG: Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).Immunoglobulin Switch Region: A site located in the INTRONS at the 5' end of each constant region segment of a immunoglobulin heavy-chain gene where recombination (or rearrangement) occur during IMMUNOGLOBULIN CLASS SWITCHING. Ig switch regions are found on genes encoding all five classes (IMMUNOGLOBULIN ISOTYPES) of IMMUNOGLOBULIN HEAVY CHAINS.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Complementarity Determining Regions: Three regions (CDR1; CDR2 and CDR3) of amino acid sequence in the IMMUNOGLOBULIN VARIABLE REGION that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (RECEPTORS, ANTIGEN, T-CELL).Mitogens: Substances that stimulate mitosis and lymphocyte transformation. They include not only substances associated with LECTINS, but also substances from streptococci (associated with streptolysin S) and from strains of alpha-toxin-producing staphylococci. (Stedman, 25th ed)Receptors, Fc: Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.Binding Sites, Antibody: Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.Antigens, CD95: A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Lymphoproliferative Disorders: Disorders characterized by proliferation of lymphoid tissue, general or unspecified.Radiation Chimera: An organism whose body contains cell populations of different genotypes as a result of the TRANSPLANTATION of donor cells after sufficient ionizing radiation to destroy the mature recipient's cells which would otherwise reject the donor cells.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Muramidase: A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17.Mice, Inbred C3HDNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Antigens, Differentiation: Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.Immunoglobulin alpha-Chains: The class of heavy chains found in IMMUNOGLOBULIN A. They have a molecular weight of approximately 58 kDa and contain about 470 amino acid residues arranged in four domains and an oligosaccharide component bound covalently to their Fc fragment constant region.Immunologic Capping: An energy dependent process following the crosslinking of B CELL ANTIGEN RECEPTORS by multivalent ligands (bivalent anti-antibodies, LECTINS or ANTIGENS), on the B-cell surface. The crosslinked ligand-antigen receptor complexes collect in patches which flow to and aggregate at one pole of the cell to form a large mass - the cap. The caps may then be endocytosed or shed into the environment.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Mice, Inbred DBAMembrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.Lymphoma, Large B-Cell, Diffuse: Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.gamma-Globulins: Serum globulins that migrate to the gamma region (most positively charged) upon ELECTROPHORESIS. At one time, gamma-globulins came to be used as a synonym for immunoglobulins since most immunoglobulins are gamma globulins and conversely most gamma globulins are immunoglobulins. But since some immunoglobulins exhibit an alpha or beta electrophoretic mobility, that usage is in decline.Immunoglobulin Constant Regions: The domains of the immunoglobulin molecules that are invariable in their amino acid sequence within any class or subclass of immunoglobulin. They confer biological as well as structural functions to immunoglobulins. One each on both the light chains and the heavy chains comprises the C-terminus half of the IMMUNOGLOBULIN FAB FRAGMENT and two or three of them make up the rest of the heavy chains (all of the IMMUNOGLOBULIN FC FRAGMENT)Adjuvants, Immunologic: Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.Epstein-Barr Virus Infections: Infection with human herpesvirus 4 (HERPESVIRUS 4, HUMAN); which may facilitate the development of various lymphoproliferative disorders. These include BURKITT LYMPHOMA (African type), INFECTIOUS MONONUCLEOSIS, and oral hairy leukoplakia (LEUKOPLAKIA, HAIRY).

TALL-1 is a novel member of the TNF family that is down-regulated by mitogens. (1/494)

Members of the tumor necrosis factor (TNF) family play important roles in modulation of immune responses. We describe the identification and cloning of a novel TNF family member that has been designated as TALL-1. TALL-1 is a 285-amino acid type II transmembrane protein. Its carboxy terminus shares approximately 35% sequence identity with the recently identified APRIL and approximately 20-25% with TNF, FasL, TRAIL, and lymphotoxin-alpha, suggesting that TALL-1 and APRIL belong to a subfamily of the TNF family of ligands. Northern blot analysis suggests that TALL-1 is expressed abundantly in peripheral blood leukocytes and weakly in spleen but is barely detectable in all other tissues examined. Reverse transcriptase-polymerase chain reaction analysis indicates that TALL-1 is specifically expressed in monocytes and macrophages but is undetectable in T and B lymphocytes. Furthermore, TALL-1 expression is dramatically down-regulated by phorbol myristate acetate/ionomycin.  (+info)

Identification and characterization of a novel cytokine, THANK, a TNF homologue that activates apoptosis, nuclear factor-kappaB, and c-Jun NH2-terminal kinase. (2/494)

By using the amino acid sequence motif of tumor necrosis factor (TNF), we searched the expressed sequence tag data base and identified a novel full-length cDNA encoding 285 amino acid residues and named it THANK. THANK is a type II transmembrane protein with 15-20% overall amino acid sequence homology to TNF, LT-alpha, FasL, and LIGHT, all members of the TNF family. The mRNA for THANK was expressed at high levels by peripheral blood leukocytes, lymph node, spleen, and thymus and at low levels by small intestine, pancreas, placenta, and lungs. THANK was also prominently expressed in hematopoietic cell lines. The recombinant purified protein expressed in the baculovirus system had an approximate molecular size 20 kDa with amino-terminal sequence of AVQGP. Treatment of human myeloid U937 cells with purified THANK activated nuclear transcription factor-kappaB (NF-kappaB) consisting of p50 and p65. Activation was time- and dose-dependent, beginning with as little as a 1 pM amount of the cytokines and as early as 15 min. Under the same conditions, THANK also activated c-jun NH2-terminal kinase (JNK) in U937 cells. THANK also strongly suppressed the growth of tumor cell lines and activated caspase-3. Although THANK had all the activities and potency of TNF, it did not bind to the TNF receptors. Thus our results indicate that THANK is a novel cytokine that belongs to the TNF family and activates apoptosis, NF-kappaB, and JNK through a distinct receptor.  (+info)

BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. (3/494)

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M-stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center-like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.  (+info)

BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. (4/494)

The tumor necrosis factor (TNF) superfamily of cytokines includes both soluble and membrane-bound proteins that regulate immune responses. A member of the human TNF family, BLyS (B lymphocyte stimulator), was identified that induced B cell proliferation and immunoglobulin secretion. BLyS expression on human monocytes could be up-regulated by interferon-gamma. Soluble BLyS functioned as a potent B cell growth factor in costimulation assays. Administration of soluble recombinant BLyS to mice disrupted splenic B and T cell zones and resulted in elevated serum immunoglobulin concentrations. The B cell tropism of BLyS is consistent with its receptor expression on B-lineage cells. The biological profile of BLyS suggests it is involved in monocyte-driven B cell activation.  (+info)

Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. (5/494)

The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti-DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.  (+info)

Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. (6/494)

TALL-1/Blys/BAFF is a member of the tumor necrosis factor (TNF) ligand superfamily that is functionally involved in B cell proliferation. Here, we describe B cell hyperplasia and autoimmune lupus-like changes in transgenic mice expressing TALL-1 under the control of a beta-actin promoter. The TALL-1 transgenic mice showed severe enlargement of spleen, lymph nodes, and Peyer's patches because of an increased number of B220+ cells. The transgenic mice also had hypergammaglobulinemia contributed by elevations of serum IgM, IgG, IgA, and IgE. In addition, a phenotype similar to autoimmune lupus-like disease was also seen in TALL-1 transgenic mice, characterized by the presence of autoantibodies to nuclear antigens and immune complex deposits in the kidney. Prolonged survival and hyperactivity of transgenic B cells may contribute to the autoimmune lupus-like phenotype in these animals. Our studies further confirm TALL-1 as a stimulator of B cells that affect Ig production. Thus, TALL-1 may be a primary mediator in B cell-associated autoimmune diseases.  (+info)

BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population. (7/494)

The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor-triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.  (+info)

TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation. (8/494)

We and others recently reported tumor necrosis factor (TNF) and apoptosis ligand-related leukocyte-expressed ligand 1 (TALL-1) as a novel member of the TNF ligand family that is functionally involved in B cell proliferation. Transgenic mice overexpressing TALL-1 have severe B cell hyperplasia and lupus-like autoimmune disease. Here, we describe expression cloning of a cell surface receptor for TALL-1 from a human Burkitt's lymphoma RAJI cell library. The cloned receptor is identical to the previously reported TNF receptor (TNFR) homologue transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). Murine TACI was subsequently isolated from the mouse B lymphoma A20 cells. Human and murine TACI share 54% identity overall. Human TACI exhibits high binding affinities to both human and murine TALL-1. Soluble TACI extracellular domain protein specifically blocks TALL-1-mediated B cell proliferation without affecting CD40- or lipopolysaccharide-mediated B cell proliferation in vitro. In addition, when injected into mice, soluble TACI inhibits antibody production to both T cell-dependent and -independent antigens. By yeast two-hybrid screening of a B cell library with TACI intracellular domain, we identified that, like many other TNFR family members, TACI intracellular domain interacts with TNFR-associated factor (TRAF)2, 5, and 6. Correspondingly, TACI activation in a B cell line results in nuclear factor kappaB and c-Jun NH(2)-terminal kinase activation. The identification and characterization of the receptor for TALL-1 provides useful information for the development of a treatment for B cell-mediated autoimmune diseases such as systemic lupus erythematosus.  (+info)

*B-cell activating factor

... (BAFF) also known as tumor necrosis factor ligand superfamily member 13B is a protein that in humans ... "Elevated B cell-activating factor of the tumour necrosis factor family in coeliac disease". Scandinavian Journal of ... B-Cell Activating Factor at the US National Library of Medicine Medical Subject Headings (MeSH) Human DTL genome location and ... PMC 3723786 . Lied GA, Lillestøl K, Valeur J, Berstad A (July 2010). "Intestinal B cell-activating factor: an indicator of non- ...

*Anthera Pharmaceuticals

Blisibimod is a selective peptibody antagonist of B-cell activating factor (BAFF). BAFF is critical to the development, ... "A novel modality of BAFF-specific inhibitor AMG623 peptibody reduces B-cell number and improves outcomes in murine models of ... It is primarily expressed by macrophages, monocytes and dendritic cells. Blisibimod binds to BAFF and inhibits the interaction ... "Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren's syndrome". J Clin Invest. 109 (1): 59 ...

*APRIL (protein)

TNFSF13 has been shown to interact with TNFRSF13B and B-cell activating factor. APRIL is being explored as a target for ... a new ligand of the tumor necrosis factor family, stimulates tumor cell growth". The Journal of Experimental Medicine. 188 (6 ... a new member of the tumor necrosis factor family, modulates death ligand-induced apoptosis". Cell Death and Differentiation. 8 ... The protein encoded by this gene is a member of the tumor necrosis factor ligand (TNF) ligand family. This protein is a ligand ...

*Heterozygote advantage

B-cell activating factor (BAFF) is a cytokine encoded by the TNFSF13B gene. A variant of the gene containing a deletion (GCTGT ... When a sufferer's red blood cells are exposed to low-oxygen conditions, the cells lose their healthy round shape and become ... In carriers, this drop is sufficient to trigger the full sickle-cell reaction, which leads to infected cells being rapidly ... yet will still possess a sickle cell trait, whereby some of the red blood cells undergo benign effects of SCA, but nothing ...

*Transmembrane activator and CAML interactor

TNFRSF13B has been shown to interact with B-cell activating factor, TRAF6, TRAF5, TNFSF13, TRAF2 and CAMLG. GRCh38: Ensembl ... TACI controls T cell-independent B cell antibody responses, isotype switching, and B cell homeostasis. TACI mutations are ... a tumor necrosis factor family member involved in B cell regulation". The Journal of Experimental Medicine. 192 (1): 137-43. ... a tumor necrosis factor family member involved in B cell regulation". The Journal of Experimental Medicine. 192 (1): 137-43. ...

*B-cell maturation antigen

TNFRSF17 is a cell surface receptor of the TNF receptor superfamily which recognizes B-cell activating factor (BAFF). The ... TNFRSF17 has been shown to interact with the B-cell activating factor TNFSF13B. A conserved domain at the N-terminus, BCMA TALL ... B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c ... B-cell maturation antigen (BCMA or BCM), also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17), is a ...

*Belimumab

... and survival factors protect them from cell suicide. B-cell activating factor (BAFF), also called B-lymphocyte stimulator (BLyS ... B lymphocytes (B cells) are one of the immune cells responsible for the damage in autoimmune disease. B cells develop in the ... B-cell activating factor is a naturally occurring protein that was discovered by researchers from National Jewish Health ( ... is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS). B ...

*BAFF receptor

B-cell activating factor (BAFF) enhances B-cell survival in vitro and is a regulator of the peripheral B-cell population. The ... BAFF receptor (B-cell activating factor receptor, BAFF-R), also known as tumor necrosis factor receptor superfamily member 13C ... Rolink AG, Melchers F (Apr 2002). "BAFFled B cells survive and thrive: roles of BAFF in B-cell development". Current Opinion in ... a novel ligand of the tumor necrosis factor family, stimulates B cell growth". The Journal of Experimental Medicine. 189 (11): ...

*ERBB3

... kinase pathway is a dominant growth factor-activated cell survival pathway in LNCaP human prostate carcinoma cells". Cancer Res ... 1993). "Characterization of a breast cancer cell differentiation factor that specifically activates the HER4/p180erbB4 receptor ... Epidermal growth factor receptor family Epidermal growth factor receptor Receptor tyrosine-kinases GRCh38: Ensembl release 89: ... "Insulin-like growth factor-1 receptor inhibition induces a resistance mechanism via the epidermal growth factor receptor/HER3/ ...

*PIK3R1

... kinase pathway is a dominant growth factor-activated cell survival pathway in LNCaP human prostate carcinoma cells". Cancer Res ... "Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells". ... linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells". Biochem. J. 356 ( ... "Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras". Cell. 89 (3): 457-67 ...

*Versican

"Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis". Nature. 457 (7225): 102-6. doi:10.1038 ... Smooth muscle cells of blood vessels, epithelial cells of skin, and the cells of central and peripheral nervous system are a ... acting via TLR2 to activate myeloid cells and produce TNF-alpha. Versican is increased in the changing tissue extracellular ... large family of cell adhesion molecules) with their cell surface receptors is sterically hindered. Expression of versican is ...

*Tabalumab

... (LY 2127399) is an anti-B-cell activating factor (BAFF) human monoclonal antibody designed for the treatment of ... autoimmune diseases and B cell malignancies. Tabalumab was developed by Eli Lilly and Company. A phase III clinical trial for ...

*Prostaglandin F receptor

RAF/MEK/Mitogen-activated protein kinases; PKC/Ca2+/Calcineurin/Nuclear factor of activated T-cells; and the EGF cellular ... In certain cells, activation of FP also stimulates G12/G13-Gβγ G proteins to activate the Rho family of GTPases signaling ... In particular, Gq stimulates cell signal pathways involving a) phospholipase C/IP3/cell Ca2+ mobilization/diacylglycerol/ ... regulation of proliferation by activation of the epidermal growth factor receptor and mitogen-activated protein kinase ...

*MSC (gene)

"Assignment of the human helix-loop-helix transcription factor gene musculin/activated B-cell factor-1 (MSC) to chromosome 8q21 ... Knight JC, Keating BJ, Kwiatkowski DP (2004). "Allele-specific repression of lymphotoxin-alpha by activated B cell factor-1". ... "Entrez Gene: MSC musculin (activated B-cell factor-1)". Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction ... a Novel Basic Helix-Loop-Helix Transcription Factor Expressed in Activated B Lymphocytes". Mol Cell Biol. 18 (6): 3130-9. PMC ...

*Mothers against decapentaplegic homolog 6

"Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells". Cytokine Growth ... Datta PK, Moses HL (2000). "STRAP and Smad7 Synergize in the Inhibition of Transforming Growth Factor β Signaling". Mol. Cell. ... "Regulation of transforming growth factor-beta signaling by protein inhibitor of activated STAT, PIASy through Smad3". J. Biol. ... Like many other TGFβ family members SMAD6 is involved in cell signalling. It acts as a regulator of TGFβ family (such as bone ...

*Mothers against decapentaplegic homolog 4

"Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells". Cytokine & Growth ... PP2A-dependent apoptotic effect of exogenous transforming growth factor beta 1 in lymphoma cells". Experimental Cell Research. ... SMAD4 serves as a mediator between extracellular growth factors from the TGFβ family and genes inside the cell nucleus. The ... Intracellular reactions involving SMAD4 are triggered by the binding, on the surface of the cells, of growth factors from the ...

*Mothers against decapentaplegic homolog 2

"Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells". Cytokine Growth ... with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor ... superfamily of growth factors into the cell nucleus. Binding of a subgroup of TGFβ superfamily ligands to extracellular ... "FAST-2 Is a Mammalian Winged-Helix Protein Which Mediates Transforming Growth Factor β Signals". Mol. Cell. Biol. 19 (1): 424- ...

*Mothers against decapentaplegic homolog 7

"Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells". Cytokine Growth ... of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-beta-activated kinase 1 and mitogen-activated ... "Smad7 acts as a negative regulator of the epidermal growth factor (EGF) signaling pathway in breast cancer cells". Cancer Lett ... "Regulation of transforming growth factor-beta signaling by protein inhibitor of activated STAT, PIASy through Smad3". J. Biol. ...

*Mothers against decapentaplegic homolog 3

"Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells". Cytokine & Growth ... These complexes are recruited to sites throughout the genome by cell lineage-defining transcription factors (LDTFs) that ... Shi, Yigong; Massagué, Joan (2003). "Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus". Cell. 113 (6): 685-700. ... PTTG1 has been associated with various cancer cells including prostate cancer cells. Studies showed that the overexpression of ...

*NFAT5

Nuclear factor of activated T-cells 5, also known as NFAT5, is a human gene that encodes a transcription factor that regulates ... The product of this gene is a member of the nuclear factors of activated T cells (NFAT) family of transcription factors. ... NFAT5 nuclear factor of activated T-cells 5, tonicity-responsive". Lee SD, Choi SY, Lim SW, Lamitina ST, Ho SN, Go WY, Kwon HM ... "Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT". Mol. Cell. 20 (4): 539-50. doi: ...

*PIK3CB

Sotsios Y, Whittaker GC, Westwick J, Ward SG (1999). "The CXC chemokine stromal cell-derived factor activates a Gi-coupled ... 2001). "HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a ... "Extracellular human immunodeficiency virus type-1 Tat protein activates phosphatidylinositol 3-kinase in PC12 neuronal cells". ... Cell. Biol. 14 (4): 2577-83. doi:10.1128/mcb.14.4.2577. PMC 358625 . PMID 8139559. Milani D, Mazzoni M, Borgatti P, et al. ( ...

*NFATC4

Nuclear factor of activated T-cells, cytoplasmic 4 is a protein that in humans is encoded by the NFATC4 gene. The product of ... Other members of this family of nuclear factors of activated T cells also participate in the formation of this complex. The ... "Entrez Gene: NFATC4 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4". Fougère M, Gaudineau B, Barbier ... this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of ...

*NFATC2

"Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: ... Nuclear factor of activated T-cells, cytoplasmic 2 is a protein that in humans is encoded by the NFATC2 gene. This gene is a ... San-Antonio B, Iñiguez MA, Fresno M (Jul 2002). "Protein kinase Czeta phosphorylates nuclear factor of activated T cells and ... García-Rodríguez C, Rao A (Jun 1998). "Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the ...

*NFATC3

Nuclear factor of activated T-cells, cytoplasmic 3 is a protein that in humans is encoded by the NFATC3 gene. The product of ... "Entrez Gene: NFATC3 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3". Rao A, Luo C, Hogan PG (1997 ... a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus". Molecular and ... this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of ...

*NFATC1

"Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells". Cell. 95 (5): 595-604. doi:10.1016/ ... Nuclear factor of activated T-cells, cytoplasmic 1 is a protein that in humans is encoded by the NFATC1 gene. The product of ... Park J, Takeuchi A, Sharma S (Aug 1996). "Characterization of a new isoform of the NFAT (nuclear factor of activated T cells) ... "Entrez Gene: NFATC1 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1". Rainio EM, Sandholm J, Koskinen ...

*G1 phase

In order for the cell to continue through the G1-pm, there must be a high amount of growth factors and a steady rate of protein ... These complexes then activate S-Cdk complexes that move forward with DNA replication in the S phase. Concurrently, anaphase- ... but it changes the course of the cell. After a vertebrate cell has been in the G1 phase for about three hours, the cell enters ... G1 phase and the other subphases of the cell cycle may be affected by limiting growth factors such as nutrient supply, ...
Objective: To assess the effects of tumour necrosis factor (TNF) antagonist therapy on B lymphocyte stimulator (BLyS) expression in patients with rheumatoid arthritis (RA).. Methods: Blood from 38 patients with RA from a single centre was collected prior to and following initiation of TNF antagonist therapy. Plasma BLyS protein levels, blood leukocyte BLyS mRNA levels and disease activity were longitudinally monitored. Twelve patients with RA who either refused or were felt not to be candidates for TNF antagonist therapy and five normal healthy volunteers served as TNF antagonist-naïve controls.. Results: Baseline plasma BLyS protein levels, but not blood leukocyte BLyS mRNA levels, were elevated in patients with RA. Plasma BLyS protein levels declined following initiation of TNF antagonist therapy in good responders (GR) to TNF antagonist therapy but not in poor responders (PR). By contrast, the erythrocyte sedimentation rate (ESR) declined in response to TNF antagonist therapy in GR and PR. ...
B cell-activating factor belonging to the TNF family (BAFF) and its receptor BAFF-R play critical roles in the maturation and survival of conventional peripheral B cells. However, they appeared to be dispensable for the generation and maintenance of CD5(+) B-1 cells as BAFF(-/-) and BAFF-R(-/-) mice have normal B-1 cell populations. Hence, it is presently unclear if B-1 cells are responsive to BAFF and if BAFF regulates some aspects of B-1 cell function. We show here that BAFF-R and transmembrane activator and CAML interactor (TACI) are the major receptors expressed by B-1 cells. Specifically, we show that BAFF treatment of B-1 cells leads to increased NF-kappaB p100 processing and CD21/CD35 expression. Interestingly, toll-like receptor (TLR) engagement of B-1 cells augmented the surface expression of BAFF receptors and rendered them responsive to BAFF costimulation, as evidenced by their increased proliferation, expression of cell surface activation markers and secretion of the pro-inflammatory
Measure human BAFF/BLyS in cell culture supernates, serum, and plasma with our highly sensitive BAFF/BLyS/TNFSF13B Quantikine ELISA Kit.
B lymphocyte stimulator (BLyS) controls the proportion of transitional B cells completing differentiation and the longevity of most primary B cells. These key roles in B cell selection, survival and homeostasis make BLyS and its receptors attractive candidates for targeted B cell therapeutics. Here we have used a neutralizing hamster anti-mouse BLyS antibody to assess how BLyS depletion influences developing and primary B cell subsets, as well as how this treatment impacts primary TD and TI immune responses. Mice treated with 10F4 show rapid and substantial reductions in the transitional, follicular, and marginal zone pools which persist for ~40 days. In contrast, the only bone marrow subset affected is the mature recirculating B cell fraction. Interestingly, splenic B1 cells, but not peritoneal B1 cells, are reduced as well. Following the recovery of serum BLyS levels, peripheral reconstitution occurs gradually, such that normal B cell numbers return by day 70-80. Mice challenged with ...
Naive peripheral B cells survive in vivo because of active stimulation by the TNF superfamily ligand B lymphocyte stimulator (BLyS/BAFF). Although the survival promoting properties of BLyS are well known, the signal pathways and molecular effectors that characterize this stimulation are still being elucidated. In this communication, we discuss the signal cascades that effect BLyS dependent survival and the regulation of BLyS induced signaling. We also examine the role of BLyS as a growth factor and propose that BLyS induced metabolic enhancement optimizes the B cell response to BCR and TLR-dependent signaling.
Mice were rendered specifically tolerant to the fluorescein isothiocyanatedextran (FITC) epitope by injection of FITC-dextran B512. Their spleen cells were removed at various times and cultivated in vitro with different polyclonal B-cell activators, such as lipopolysaccharide (LPS), purified protein derivative of tuberculin, and native dextran. LPS caused the appearance of high affinity anti-FITC plaque-forming cells to an equal extent with cells from untreated and tolerant animals, whereas native dextran failed to activate cells from tolerant mice, although it was a potent activator of normal cells. It was concluded that tolerance induction only affects those B cells that could respond to the polyclonal B-cell-activating properties of the tolerogen, but not other B cells having an identical set of Ig receptors directed against the tolerogen. ...
B lymphocyte stimulator (BLyS) is a factor determining the survival of B cells, and elevated levels in serum or locally have been observed in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. Belimumab (LymphoStat-B), a human monoclonal antibody that inhibits BlyS, was developed for the treatment of these diseases. OBJECTIVE: To summarize preclinical development, efficacy and safety of belimumab in treatment of RA and SLE. METHODS: Articles found in a PubMed search and data presented in abstract form at international conferences up to August 2008 are described. RESULTS/CONCLUSIONS: Belimumab was well tolerated in treatment of RA over 24 weeks and SLE over 3 years. It significantly decreased rheumatoid factor (RF) levels, and modestly reduced symptoms of RA, especially in some subgroups such as patients with high disease activity, positive RF and no anti-TNF treatment experience. It also significantly reduced symptoms of SLE, and decreased anti-double-stranded DNA ...
Increased Ig, RF, and CIC levels in BAFF-Tg mice. (A) Reduced SDS-PAGE of sera from five control littermates and nine BAFF-Tg mice showing that BAFF increases I
The samples used in this paper were obtained from patients with osteoarthritis (OA) or RA during knee-TEP operations. First of all, expression of the known BAFF-binding receptors BCMA, TACI and BAFF-R was analyzed in SF of patients with OA and RA using flow cytometry and immunohistochemistry. In a further step, the influence of several stimulants, including cytokines, TLR-agonists and cell activators on receptor expression was tested. Finally, taking into account BAFF function in other cell types, SF were stimulated with BAFF and stained with Annexin V in order to analyze its effect on apoptosis in SF ...
BAFF belongs to the tumor necrosis factor (TNF) family, and its downstream signaling plays a critical role in B-cell survival and maturation.
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BAFF大鼠单克隆抗体[Buffy 2](ab16081)可与小鼠, 人样本反应并经WB, IHC, Flow Cyt实验严格验证,被13篇文献引用。所有产品均提供质保服务,中国75%以上现货。
BLyS Human Recombinant fused to His tag at N-terminus produced in E.Coli is a single, non-glycosylated polypeptide chain containing 190 amino acids and having a molecular mass of 21 kDa.
Background The TNF superfamily member B lymphocyte stimulator (BLyS), referred to as BAFF, is known to be an effective modulator of peripheral B cell homeostasis that promotes B cell survival and differentiation. BLyS is expressed by a few stromal cells, T cells, and most myeloid cell. BLyS transgenic mice show an expansion of the peripheral mature B cell compartment, hyperglobulinemia, anti-single-stranded DNA and anti-double-stranded DNA antibodies, and circulating immune complexes. A proliferation-inducing ligand (APRIL) is a homolog to BLyS that is expressed by monocytes, macrophages, DCs, T cells, and others. APRIL is virtually undetectable in normal tissues but is strongly expressed in adenocarcinomas and can accelerate the growth of malignant cells in vitro and in vivo. APRIL/BLyS heterotrimers are present in the serum of patients with systemic autoimmune diseases like rheumatoid arthritis (RA), SLE, and SS. APRIL over expression promotes a strong survival signal for both CD4+ and CD8+ T ...
B cell maturation starts in the bone marrow but is completed in the spleen (Hardy et al., 2007). Survival of IgM+ splenic B cells is linked to the antiapoptotic B cell lymphoma 2 (BCL2) family of proteins and their opposing proapoptotic antagonist, BCL2-interacting mediator of cell death (BIM; Enders et al., 2003), and depends on "tonic" signals from surface IgM and IgD B cell antigen receptors transmitted through spleen tyrosine kinase (SYK), Brutons tyrosine kinase (BTK), and phosphatidylinositol 3 kinase (Srinivasan et al., 2009). Starting from the transitional 2 (T2) stage, B cells also depend on survival signals provided by a circulating cytokine, B cell-activating factor (BAFF), engaging the BAFF receptor (BAFFR; Khan, 2009). BCRs and BAFFR signal via pathways that activate transcription factors of the NF-κB family, and these play essential roles in mediating survival of B cells (Siebenlist et al., 2005).. CD74, also called MHC II invariant chain or Ii, is a type 2 transmembrane protein ...
Results: Salivary BAFF levels (median: 12.39 ng/ml) were significantly decreased by using HQ both at 12 (2.78 ng/ml, P = 0.008) and 24 weeks (0.54 ng/ml, P = 0.011). Similarly, decreases in serum BAFF levels (5.23 ng/ml) were seen at 12 and 24 weeks after HQ treatment (2.18 ng/ml, P = 0.008 and 0.0 ng/ml, P = 0.012, respectively). Serum and salivary BAFF levels were significantly lower in healthy controls (0.37 ng/ml and 0.0 ng/ml, resp.) compared to those of pSS before HQ therapy (P = 0.006 and P = 0.001, resp.). Unstimulated salivary flows were similar in patients treated with HQ after 12 (0.38 ml/min) and 24 weeks (0.50 ml/min) (P = 0.51) but higher than the patients rate at baseline (0.04 ml/min) (P = 0.008 ...
The causes and mechanisms of late-onset neutropenia (LON) following rituximab treatment in patients with rheumatic diseases are not known. In this study, we aimed to investigate the role of established Fcγ receptor gene (FCGR) polymorphisms and B-cell-activating factor (BAFF) gene promoter polymorphisms for the development of LON and for the efficacy of rituximab in patients with rheumatic diseases. A single-center case-control retrospective study was nested in a cohort of 214 consecutive patients with rheumatic diseases treated with rituximab. Eleven patients presented with LON. Fifty non-LON control subjects were matched by diagnosis, age, sex, and treatments. Single-nucleotide polymorphisms of FCGR (FCGR2A 131H/R, FCGR2B 232I/T, FCGR3A 158V/F) and BAFF promoter polymorphism −871C/T were analyzed with polymerase chain reaction-based techniques, and serum immunoglobulin M (IgM) and BAFF levels were analyzed by enzyme-linked immunosorbent assay. Flare-free survival was related to LON occurrence and
Belimumab (also known as Benlysta™) is currently being studied in Phase III clinical trials to determine whether or not it is effective for lupus. Belimumab specifically reduces the actions of a protein called "B lymphocyte stimulator," or BLyS. BLyS is a protein that increases the lifespan and inflammatory potential of certain immune cells called B cells, which are known to be hyperactive in lupus patients. Belimumab, which interferes with BLyS, is a human antibody. This means that it looks a lot like the antibodies that the immune system makes to fight off viruses. But in this case, belimumab targets only the protein BLyS. Because it only has one target, it is called a "monoclonal" antibody ...
Follicular B cell survival requires signaling from BAFFR, a receptor for BAFF and the B cell antigen receptor (BCR). This tonic BCR survival signal is distinct from that induced by antigen binding and may be ligand-independent. We show that inducible inactivation of the Syk tyrosine kinase, a key signal transducer from the BCR following antigen binding, resulted in the death of most follicular B cells because Syk-deficient cells were unable to survive in response to BAFF. Genetic rescue studies demonstrated that Syk transduces BAFFR survival signals via ERK and PI3 kinase. Surprisingly, BAFFR signaling directly induced phosphorylation of both Syk and the BCR-associated Igα signaling subunit, and this Syk phosphorylation required the BCR. We conclude that the BCR and Igα may be required for B cell survival because they function as adaptor proteins in a BAFFR signaling pathway leading to activation of Syk, demonstrating previously unrecognized crosstalk between the two receptors. ...
Results SLEDAI-2K (median baseline score: 8.0; IQR: 4.0-13.8), PGA and corticosteroid use decreased during therapy, and patients reported improvements on fatigue, pain, and general health (p,0.0001 for all). SDI scores remained stable (p=0.08). Patients with baseline SDI scores,1 showed decreased probability and prolonged time to attain SRI response (HR: 0.449; 95% CI: 0.208-0.967), as did current smokers compared with non-smokers (HR: 0.103; 95% CI: 0.025-0.427). In contrast, baseline BLyS levels≥1.2 ng/mL predicted increased probability and shorter time to attain SRI response (HR: 2.566; 95% CI: 1.222-5.387). ...
Background: Belimumab, a monoclonal antibody that inhibits B-lymphocyte stimulating protein, was the first biologic agent approved for, and the first drug approved in 55 years for, the treatment of systemic lupus erythematosus (SLE) by the US Food and Drug Administration (FDA). Objective: This article reviews the current research on belimumab and provides recommendations on its use in the treatment of SLE. Methods: The Cochrane Library, EBSCO, IPA, MEDLINE, and SCOPUS were searched for research published from January 2000 to November 2011, using the search terms belimumab, Benlysta, and Lympho-Stat B. Selection criteria included peer-reviewed original research articles on the pharmacology, pharmacokinetic properties, drug interactions, and clinical efficacy and tolerability of belimumab in the treatment of SLE. Abstracts from the annual meetings of major rheumatology medical organizations and societies were searched and reviewed for new content. Additional information on belimumab was obtained from the
vessels, giving the hystologic picture of leukocytoclastic vasculitis. Clinically, this inflammation is manifested as arthralgias, fatigue, and lesions mainly in skin, kidneys and peripheral nerves, however, any organ system can be involved. Most of the so far reported clinical and laboratory investigations deal with mixed CG in chronic hepatitis C virus (HCV) infection while the data concerning essential CG vasculitis (CV) are scarce. Only recently, so-called noninfectious CV has attracted more attention of the medical community. Chronic antigenic stimulation, increased cytokine and growth factor (BLyS) levels and complement activation may are implicated in the pathogenesis of CV, etiology of which remains largely unknown. Objectives: To investigate clinical and imunoserologic characteristics of patients with CG and their relation to presence and clinical manifestations of vasculitis, as well as to the etiology of CG; explore quantitative and qualitative characteristics of cryoG; to analyze a ...
The cumulative prednisone dose over 52 weeks also was lower in the belimumab group, at a median of 4,190 mg, compared with the placebo group, at 4,758.1 mg (P=0.0005). "This study builds on findings from previous studies, which suggest that belimumab has a corticosteroid-sparing effect," they noted.. With regard to safety, the overall rate of adverse events was similar in the belimumab and placebo groups, and while the incidence rate of serious adverse events was higher in the placebo group (18.3% versus 12.3%), the rate of infectious serious adverse events was similar (5.3% and 5.5%).. The investigators also considered adverse events of special interest, including malignancies, post-infusion systemic reactions, depression/suicide/self injury, and deaths, finding similar rates between the belimumab and placebo groups. In the belimumab group, there were no suicide attempts or completed suicides, although there was one case of suicidal ideation. In the placebo group, there was one suicide ...
Belimumab 10 mg/kg IV plus oral azathioprine 2 mg/kg/day; belimumab administered on Days 0, 14, 28, and then every 28 days until the end of the study. If the results in the double-blind period show that belimumab is safe and effective, then participants have the option to continue treatment with belimumab in a 6-month open-label extension phase. Patients who opt to participate in the extension will continue to receive belimumab 10 mg/kg IV every 28 plus oral azathioprine 2 mg/kg/day days for an additional 6 months ...
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PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The cytokine BAFF is produced by a number of cell types, including monocytes, neutrophils, macrophages, dendritic cells, and some subsets of T cells (17). Receptors for BAFF, however, were initially thought to be restricted to more differentiated B-lineage cells. Therefore, the expression of BAFF receptors on transformed B-lineage lymphocytes in CLL was not entirely unexpected. In contrast, based on BAFF-null and BAFF-R-null mutants as well as other studies, it has been generally accepted that precursor B-lineage cells do not express this receptor. Our studies confirm that there is no expression of this receptor in normal bone marrow pre-B cells. Interestingly, Rodig and colleagues (35) also performed FACS on two pre-B ALL samples and reported that these were negative for expression of BAFF-R. Therefore, the prominent expression of the BAFF-R that we detected on both Ph-positive and Ph-negative ALL samples was unanticipated. In fact, all 12 samples that were tested by us, including original ALL ...
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Recombinant Mouse BAFF (carrier-free) - BAFF is a TNF cytokine member (a type II membrane protein) that acts in both a membrane-bound form and soluble cytokine form.
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Toda la información sobre las últimas publicaciones científicas de la Clínica Universidad de Navarra. Increased expression of A Proliferation-inducing Ligand (APRIL) in lung leukocytes and alveolar epithelial cells in COPD patients with non small cell lung cancer
The autoimmune exocrinopathy Sjögrens syndrome (SS) is characterized by mononuclear cell (MNC) infiltrates of exocrine glands and overactivity of B lymphocytes. Although T cells have long been perceived as the prime effectors, increasing evidence indicates that the key role is rather served by B cells. Among related abnormalities are rheumatoid factor (RF), anti-SSA/Ro, and anti-SSB/La antibodies (Ab). Also, supporting this view is our finding of an increase in the number of circulating naïve mature B (Bm) cells, with a reciprocal decrease in that of memory B cells. Furthermore, a ratio of Bm2-plus-Bm2 cells to early Bm5-plus-late Bm5 above 5 is diagnostic. This variation partly reflects the migration of active memory B cells into the exocrine glands of the patients, as well as into their skin. More recently, the B-cell-activating factor of the TNF family (BAFF) has been endorsed with a pivotal role in B-cell survival and hence implicated in the pathogenesis of autoimmunity. In practice, B cells
Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in hypertension remains unknown. We investigated whether hypertension in mice is associated with B-cell activation and IgG production and moreover whether B-cell/IgG deficiency affords protection against hypertension and vascular remodeling. Angiotensin II (Ang II) infusion (0.7 mg/kg per day; 28 days) was associated with (1) a 25% increase in the proportion of splenic B cells expressing the activation marker CD86, (2) an 80% increase in splenic plasma cell numbers, (3) a 500% increase in circulating IgG, and (4) marked IgG accumulation in the aortic adventitia. In B-cell-activating factor receptor-deficient (BAFF-R−/−) mice, which lack mature B cells, there was no evidence of Ang II-induced increases in serum IgG. Furthermore, the hypertensive response to Ang II was attenuated in BAFF-R−/− (Δ30±4 mm Hg) relative to wild-type (Δ41±5 mm Hg) mice, and this response was ...
The maintenance of mature peripheral B cells depends on at least two survival cues, tonic signaling from the B cell receptor (BCR) complex and the extracellular cytokine B cell activating factor of the TNF family (BAFF). In addition to enhancing viability, BAFF controls the functional efficiency of the peripheral B cell pool by regulating complex physiological processes including cell growth, metabolism, energy homeostasis and entry into the cell cycle. BAFF-mediated induction of two molecular mechanisms, namely activation of the Akt signal transduction pathway and upregulation of the oncogenic kinase Pim-2 results in the modification of effector proteins including transcription factors and regulators of protein synthesis which are capable of executing the observed cellular physiological changes. The classic protein kinase C beta is instrumental in BAFF-induced Akt-activation and PKC beta-deficient B cells and mice show signs of partial refractiveness to BAFF. The protein tyrosine kinase Syk ...
Abstract 2400. Poster Board II-377. Tumor necrosis factor superfamily member BAFF-R has been shown to transduce a powerful survival signal in B lineage cells upon ligation by BAFF, its soluble high affinity ligand. The availability of BAFF in lymphoid organs and its detectable levels in the blood suggest that it is the control of receptor expression by the B cell rather than ligand production by supportive cells that limits the activity of this survival signal. The presence of BAFF-R on the surface of B cells from the transitional stages of development through maturity mirrors the expression of BAFF-R on the malignancies thought to arise from these various developmental stages and may enable B lineage malignancies to receive an anti-apoptotic signal from BAFF that reinforces and supports the expansion of the malignant cells. This additional survival signal may be crucial in indolent malignancies like chronic lymphocytic leukemia (CLL), a cancer characterized more by the prolonged survival of the ...
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BAFF and APRIL are innate immune mediators that trigger immunoglobulin G (IgG) and IgA class-switch recombination (CSR) in B cells by engaging the receptor TACI. The mechanism that underlies CSR signaling by TACI remains unknown. Here we found that the cytoplasmic domain of TACI encompasses a conserved motif that bound MyD88, an adaptor that activates transcription factor NF-kappaB signaling pathways via a Toll-interleukin 1 (IL-1) receptor (TIR) domain. TACI lacks a TIR domain, yet triggered CSR via the DNA-editing enzyme AID by activating NF-kappaB through a Toll-like receptor (TLR)-like MyD88-IRAK1-IRAK4-TRAF6-TAK1 pathway. TACI-induced CSR was impaired in mice and humans lacking MyD88 or the kinase IRAK4, which indicates that MyD88 controls a B cell-intrinsic, TIR-independent, TACI-dependent pathway for immunoglobulin diversification. ...
The number of mature B cells is carefully controlled by signalling from receptors that support B cell survival. The best studied of these are the B cell antigen receptor (BCR) and BAFFR. Recent work has shown that signalling from these receptors is closely linked, involves the CD19 co-receptor, and leads to activation of canonical and non-canonical NF-κB pathways, ERK1, ERK2 and ERK5 MAP kinases, and PI-3 kinases. Importantly, studies show that investigation of the importance of signalling molecules in cell survival requires the use of inducible gene deletions within mature B cells. This overcomes the limitations of many earlier studies using constitutive gene deletions which were unable to distinguish between requirements for a protein in development versus survival. ...
A positive immune response to at least one pneumococcal serotype is defined as a 2-fold or greater increase from pre-vaccination levels. For unquantifiable pre-vaccination antibody levels, a positive antibody response was considered as a post-vaccination level ,=0.6 micrograms (µg)/milliliter (mL). Post-vaccination pneumococcal titers were assessed on Day 28 (Week 4) prior to the first dose of belimumab in the early cohort and on Day 196 (Week 28) prior to the last belimumab dose in the late cohort. Evaluable participants for the early cohort included those who received the vaccination at Day 0 and had titers drawn at Week 4. For the late cohort, evaluable participants received at least 5 of the 7 doses of belimumab up through Week 24, received the vaccination at Week 24, and had titers drawn at Week 28 ...
We show here that approximately 25% of the mature peripheral B cells can survive in the mouse for at least 2 months without Syk, in a manner that requires BAFF‐R and CD19 signaling. In contrast, deletion of the Syk gene in early B cells results in the appearance of a small number of immature IgM+ B cells, which, however, fail to give rise to any mature B cells in the periphery (Cheng et al, 1995). Thus, pre‐B and mature B cells have different requirements for Syk. Indeed, the pre‐BCR is an autonomously signaling receptor that continuously engages Syk, whereas the BCR forms an autoinhibited oligomer on mature B cells that is not in contact with Syk. This notion is supported by a proximity ligation analysis showing that Syk is localized near the BCR only after BCR activation (Infantino et al, 2010; Klasener et al, 2014).. The presence of large amounts of Syk‐negative mature B cells in the induced mb1‐CreERT2;Sykfl/fl mice allowed us to analyze the in vivo role of this kinase in the ...
We show here that approximately 25% of the mature peripheral B cells can survive in the mouse for at least 2 months without Syk, in a manner that requires BAFF‐R and CD19 signaling. In contrast, deletion of the Syk gene in early B cells results in the appearance of a small number of immature IgM+ B cells, which, however, fail to give rise to any mature B cells in the periphery (Cheng et al, 1995). Thus, pre‐B and mature B cells have different requirements for Syk. Indeed, the pre‐BCR is an autonomously signaling receptor that continuously engages Syk, whereas the BCR forms an autoinhibited oligomer on mature B cells that is not in contact with Syk. This notion is supported by a proximity ligation analysis showing that Syk is localized near the BCR only after BCR activation (Infantino et al, 2010; Klasener et al, 2014).. The presence of large amounts of Syk‐negative mature B cells in the induced mb1‐CreERT2;Sykfl/fl mice allowed us to analyze the in vivo role of this kinase in the ...
The principle role of the company is to identify, to verify the validity and ultimately to offer a range of biochemical assays each of which will provide unique and informative results to the condition of an individual patient from which the physician can
BLyS is a fundamental survival factor for transitional and mature B cells, whereas APRIL mainly affects B-1 cell activity, humoral responses and immunoglobulin class switching.1 We recently reported that aging APRIL transgenic mice develop B-1 cell-associated tumors that are highly reminiscent of human CLL; our initial analysis showed increased levels of circulating APRIL in CLL patients (n=22) compared to healthy donors.2 Two other reports described that BLyS and APRIL can act in an autocrine manner in CLL tumor cells, promoting cell survival.3,4 In addition, APRIL produced by inflammatory cells that infiltrate tumor lesions appears to contribute to disease in B cell lymphoma.5. To further evaluate APRIL and BLyS implication in CLL, we performed a retrospective study of a cohort of 95 patients diagnosed with CLL according to NCI criteria.6 After informed consent was obtained, peripheral blood samples were collected from 1991 to 2005, aliquoted and frozen. As a control, 32 sera from age- and ...
Tumour necrosis factor family. Family of cytokines that form homotrimeric or heterotrimeric complexes. TNF mediates mature T-cell receptor-induced apoptosis through the p75 TNF receptor. ...
DESCRIPTION (provided by applicant): Brutons tyrosine kinase (Btk) is the target for mutations that cause X-linked agammaglobulinemia (XLA) in man and X-linked immunodeficiency (Xid) in mouse. Both mouse and man have reduced circulating B cells and display defective B cell survival and tolerance. These defects have been primarily attributed to Btk function in B cell antigen receptor (BCR) signaling. Preliminary data presented in this exploratory grant application demonstrate that Btk couples B-cell activation factor receptor (BAFF-R), a TNF-R family member, to the NF- kB pathway and facilitates B cell survival in response to its ligand, BAFF. Emerging evidence suggests that BAFF-R is as critical in B cell survival as BCR. As such, this proposal focuses on defining the molecular mechanisms by which Btk mediates BAFF-R signaling to NF-kB and peripheral B cell survival. Preliminary data further suggests that (i) Btk interfaces with BAFF-R via mechanisms involving TRAF2 and cIAP2, and (ii) Btk ...
Dendritic cells (DCs) play an essential role in regulation of immune responses. In the periphery, Ag presentation by DCs is critical for adaptive responses; for this reason, DCs are often targets of adjuvants that enhance vaccine responses. Activated mature DCs enhance B cell activation and differentiation by providing cytokines like BAFF and a proliferation-inducing ligand. However, the role of immature DCs in B cell tolerance is not well studied. Recently, mouse immature bone marrow-derived DCs (iBMDCs) have been shown to suppress anti-IgM-induced B cell activation. In this study, we tested the ability of mouse DCs to modulate B cell functions during TLR activation. We found that iBMDCs potently suppressed proliferation and differentiation of various B cell subsets on TLR stimulation. However, iBMDCs did not affect CD40-mediated B cell activation. Optimal suppression of B cell activation by iBMDCs required cell contact via the CD22 receptor on B cells. The B cell suppression was a property of ...
Systemic lupus erythematosus is a chronic inflammatory disease that occurs when the immune system attacks other cells and tissues in the body resulting in inflammation and damage. The heart, joints, skin, lungs, blood vessels, liver, kidneys and nervous system are commonly involved.. Benlysta (belimumab) is a B-lymphocyte stimulator (BLyS)-specific inhibitor indicated for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus who are receiving standard therapy.. Limitations of Use: the efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Benlysta has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of Benlysta is not recommended in these situations.. Setting: The type of physical site where the drug is provided. Settings include inpatient hospital, outpatient hospital, clinic office, or home-infusion. ...
This prospective, observational, single-centre trial evaluated the efficacy of belimumab as add-on to standard of care therapy in patients with systemic lupus
In an effort to develop more effective treatments for inflammatory diseases, immunologists have targeted numerous molecular pathways, but with limited success. Notable exceptions are anti-TNF agents, which have proved efficacious in a proportion of rheumatoid arthritis (RA) patients. Another TNF family member, termed BAFF (
Sandwich ELISA: In a sandwich ELISA (assuming 100μl/well), a concentration of 5.0-6.0 μg/ml of this antibody will detect at least 1000pg/ml of Recombinant Human BAFF when used with PeproTechs Biotinylated Antigen Affinity Purified anti-Human BAFF (500-P163GBT) as the detection antibody at a concentration of approximately 0.25-0.50 μg/ml. ...
Transducer of ErbB-2, 1 (TOB1) is an antiproliferative factor that belongs the tob/btg1 family. TOB1 and TOB2 have the ability to suppress cell growth in cell culture. TOB1 is phosphorylated by ribosomal S6 serine/threonine kinase. It interacts with ErbB-2 and interferes with growth suppression in B cells. TOB1 also inhibits T cell proliferation and the transcription of some cytokines, including interleukin 2 (IL-2). TOB1 is also known as TROB1, TROB, TOB, APRO6, and proliferation-inducing gene 49 (PIG49).. ...
Transducer of ErbB-2, 1 (TOB1) is an antiproliferative factor that belongs the tob/btg1 family. TOB1 and TOB2 have the ability to suppress cell growth in cell culture. TOB1 is phosphorylated by ribosomal S6 serine/threonine kinase. It interacts with ErbB-2 and interferes with growth suppression in B cells. TOB1 also inhibits T cell proliferation and the transcription of some cytokines, including interleukin 2 (IL-2). TOB1 is also known as TROB1, TROB, TOB, APRO6, and proliferation-inducing gene 49 (PIG49).. ...
Normal peripheral B cells can be activated by and cultured in interleukin 4 and anti-CD40 monoclonal antibodies. Is it possible to perform either stable or transient transfection assays in these cells ? Thanks for references if any. I am particularly interested in studying the expression of various p53 mutants ...
The desert is a place of extreme contrast, and it is often overlooked as a place to visit . March and April are the best times to witness the transformation from bare to full of bloom.
Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported
OBJECTIVE: It was recently demonstrated that synoviocytes (FLS) from rheumatoid arthritis (RA) patients express BAFF transcripts that are up-regulated by tumor necrosis factor alpha (TNFalpha) and interferon-gamma (IFNgamma). Thus, BAFF increases in RA target cells might be related to activation of the receptors of innate immunity. The purpose of this study was to determine whether ligands of Toll-like receptor 2 (TLR-2), TLR-4, TLR-9, and alpha5beta1 integrin are able to induce BAFF synthesis by RA FLS. METHODS: Quantitative reverse transcription-polymerase chain reaction analyses and enzyme-linked immunosorbent assays were performed to evaluate BAFF messenger RNA induction and BAFF release from FLS after stimulation by ligands for TLR-2, TLR-4, TLR-9, alpha5beta1 integrin (bacterial lipopeptide [BLP] palmitoyl-3-cysteine-serine-lysine-4, lipopolysaccharide [LPS], CpG, and protein I/II, respectively), TNFalpha, and IFNgamma. RESULTS: In contrast to IFNgamma, neither TNFalpha, LPS, BLP, nor CpG induced
We studied the immune functions of two patients with angioimmunoblastic lymphadenopathy (AILD) in an attempt to determine whether the B cells were primarily hyperactive or, rather, if T cell abnormalities might underlie the B cell hyperactivity observed in these patients. We found that the B cells of the AILD patients did not proliferate spontaneously, nor were they induced to proliferate excessively by fresh normal T cells. In contrast, AILD T cells induced both autologous and allogeneic B cells to proliferate and to differentiate into Ig secreting cells. Spontaneous culture supernates of T cells obtained from each patient induced substantial proliferation of B cells (B cell-activating activity) as well as proliferation in a standard costimulatory assay (B cell growth factor activity). The culture supernate of a T cell line, which was established from one patient, showed both activities. The T cell line supernate also induced Ig production by staphylococcal A Cowan-activated B cells. None of ...
We studied the immune functions of two patients with angioimmunoblastic lymphadenopathy (AILD) in an attempt to determine whether the B cells were primarily hyperactive or, rather, if T cell abnormalities might underlie the B cell hyperactivity observed in these patients. We found that the B cells of the AILD patients did not proliferate spontaneously, nor were they induced to proliferate excessively by fresh normal T cells. In contrast, AILD T cells induced both autologous and allogeneic B cells to proliferate and to differentiate into Ig secreting cells. Spontaneous culture supernates of T cells obtained from each patient induced substantial proliferation of B cells (B cell-activating activity) as well as proliferation in a standard costimulatory assay (B cell growth factor activity). The culture supernate of a T cell line, which was established from one patient, showed both activities. The T cell line supernate also induced Ig production by staphylococcal A Cowan-activated B cells. None of ...
SED021Mu, FTH1; FTHL6; PIG15; PLIF; Ferritin Heavy Chain; Apoferritin; Placenta Immunoregulatory Factor; Proliferation-Inducing Protein 15; Cell proliferation-inducing gene 15 protein | Products for research use only!
Human NGF-beta is a neurotrophic factor related to BDNF, NT-3 and NT-4. Human NGF-beta acts as a neurotrophic factor through its receptor beta-NGFR. This cytokine stimulates division and differentiation of sympathetic and embryonic sensory neurons, and is also involved in the growth and differentiation of B lymphocytes and B-cell survival. Human NGF-beta is a noncovalently disulfide-linked homodimer consisting of 121 amino acids with a MW of 2 x 13.6 kDa ...
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Lymphatic growth (lymphangiogenesis) within lymph nodes functions to promote dendritic cell entry and effector lymphocyte egress in response to infection or inflammation. Here we demonstrate a crucial role for lymphotoxin-beta receptor (LT beta R) signaling to fibroblastic reticular cells (FRCs) by lymphotoxin-expressing B cells in driving mesenteric lymph node lymphangiogenesis following helminth infection. LT beta R ligation on fibroblastic reticular cells leads to the production of B-cell-activating factor (BAFF), which synergized with interleukin-4 (IL-4) to promote the production of the lymphangiogenic factors, vascular endothelial growth factors (VEGF)-A and VEGF-C, by B cells. In addition, the BAFF-IL-4 synergy augments expression of lymphotoxin by antigen-activated B cells, promoting further B cell-fibroblastic reticular cell interactions. These results underlie the importance of lymphotoxin-dependent B cell-FRC cross talk in driving the expansion of lymphatic networks that function to ...
Tumor Necrosis Factor Ligand Superfamily Member 13: A member of tumor necrosis factor superfamily found on MACROPHAGES; DENDRITIC CELLS and T-LYMPHOCYTES. It occurs as transmembrane protein that can be cleaved to release a secreted form that specifically binds to TRANSMEMBRANE ACTIVATOR AND CAML INTERACTOR PROTEIN; and B CELL MATURATION ANTIGEN.
New insights into human B cell biology. B cells are highly important white blood cells known as lymphocytes and are part of the adaptive immune system. B cells have a specialised receptor on their cell surface (B cell receptor, BCR) which recognises specific proteins. Upon activation, B cells produce antibodies which bind antigens like e.g. molecules from pathogens or vaccines. The drawback of a vast range of different B cell receptors is the potential that some of the receptors recognise self-antigens which can then result in auto-immune disorders. The bone marrow continuously releases immature B cells into the blood stream. A high proportion of these so-called transitional B cells are able to recognise self-antigens via their BCR. It has been unknown where in the body these auto-reactive cells are checked and removed from the circulation. A recent publication by Anna Vossenkämper and Jo Spencer (Kings College) tracked the fate of human transitional B cells and identified that these cells ...
Update-1 BLUE Drops 1.96% and 1.77% After Hours 6/3 In the bubbly CAR-T world bluebird bio (BLUE) and Celgene announced a deal for for development of product candidates for B-cell maturation antigen (BMCA) utilizing bluebird bioss gene therapy technology to modify a patients own T-Cells to target cancer cells. A $25M up-front payment was made but […]. ...
B cells, which produce proteins called antibodies, are one type of immune cell involved in GVHD. In a paper published in the journal, Blood, a team from the University of North Carolinas Lineberger Comprehensive Cancer Center, shows in the laboratory that B cells from patients with chronic GVHD are much more active than cells from patients without the disease. The team also outlines the cell signaling pathways that contribute to this increased activity -- identifying a promising target for developing new therapies for the diseases.
Martin, VG, Wu, Y-CB, Townsend, CL, Lu, GH, OHare, JS, Mozeika, A, Coolen, AC, Kipling, D, Fraternali, F and Dunn-Walters, Deborah (2016) Transitional B cells in early human B cell development - time to revisit the paradigm? ...
A Tumor Necrosis Factor superfamily member that plays a Role in the Regulation of B-Lymphocyte Survival. It occurs as a Membrane-bound protein that is cleaved to release an biologically active soluble form with specificity to Transmembrane Activator and CAML Interactor Protein; B-Cell Activation Factor Receptor; and B-Cell Maturation Antigen ...
Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection.s profile, publications, research topics, and co-authors
If you are a society or association member and require assistance with obtaining online access instructions please contact our Journal Customer Services team ...
Original citation: J. Clin. Invest.112:286-297 (2003). doi:10.1172/JCI18025.. Citation for this corrigendum: J. Clin. Invest.113:1069 (2004). doi:10.1172/JCI18025E1.. The legends for Figures 6 and 7 contained inaccuracies, and the correct versions appear below. The conclusions of the article are unaffected.. Figure 6 BAFF increases the generation of ISC from activated memory B cells. (a and b) Memory B cells were preactivated with CD40L and IL-2/IL-10 for 4 days and then recultured with (a) media (black bars), or (b) IL-2/IL-10 alone (black bars) or in the presence of CD40L (white bars) or BAFF (gray bars). Each value represents the mean Ig secretion ± SEM of five (a) or seven (b) experiments using cells from different donors. *P , 0.05; **P , 0.01. (c) Secondary B cell cultures were performed in the absence (black bars) or presence (white bars) of soluble TACI-Ig (20 μg/ml). The values represent the mean IgA ± SD of duplicate samples. (d) Memory B cells were preactivated with ...
The amino acid and nucleic acid sequence of a protein expressed by monocytes and macrophages, called TALL-1, are disclosed. Homologues, mimetics and antibodies that bind to TALL-1 are disclosed. Also disclosed is the TALL-1 receptor, and homologues of such receptor. The invention includes methods for regulating the interaction between TALL-1 and its receptor and for identifying compounds capable of such regulation. The invention also includes methods for regulating B lymphocyte proliferation, activation, and/or survival.
notes: at this time, i always like to clarify that September and October are combined as one month. this is common practice throughout baseball when the regular season extends into the beginning of October because theres really no point in singling out October stats since so few games are played. (its the same any time the season opens up in late March; March and April are always considered one month as well.) therefore, whenever the/this month is written throughout this blog, know that i am referring to both September/October as one month despite the fact that Michael didnt play in either September or October. i have also used September/October continually in each section below even if the particular thing im discussing occurred in only one of the two months and not the other (ie. the interleague series in early September ...
The copper (I)-catalyzed alkyne azide 1,3-dipolar cycloaddition (CuAAC) or click reaction, is a highly versatile reaction that can be performed under a variety of reaction conditions including various solvents, a wide pH and temperature range, and using different copper sources, with or without additional ligands or reducing agents. This reaction is highly selective and can be performed in the presence of other functional moieties. The flexibility and selectivity has resulted in growing interest in the application of CuAAC in various fields. In this review, we briefly describe the importance of the structural folding of peptides and proteins and how the 1,4-disubstituted triazole product of the CuAAC reaction is a suitable isoster for an amide bond. However the major focus of the review is the application of this reaction to produce peptide conjugates for tagging and targeting purpose, linkers for multifunctional biomacromolecules, and reporter ions for peptide and protein analysis.
Results High expression levels of TLR7 in SLE patients positively correlated with IFN signature and disease activity, but not with BAFF titers. SLE patients with high levels of TLR7 (TLR7hi group) showed an expansion of CD19+CD38highCD24highCD10+ TR B cells. Overall, frequencies of TR B cells positively correlated with the levels of TLR7, but not TLR9. SLE patients, carrying a risk G allele, had increased TLR7 expression and TR cell frequencies, compared to non-risk allele carriers. TLR7hi SLE patients showed increased autoantibody titers and skewing towards Sm/RNP antigens. Upon IFNα priming, TR B cells up-regulated TLR7 and differentiated into plasmablasts in response to TLR7-ligand stimulation. ...
Article Countess Wear WwTW - Biostyr BAFF, United Kingdom. South West Water83 week - Programme3,570 m3/hrThe ClientSouth West Water provides water and sewerage to 1.6 million customers in Devon, Cornwall and parts of Dorset and Somerset. The region a...
Patients with systemic lupus erythematosus treated with belimumab (Benlysta) showed significant changes in immunologic biomarkers along with their clinical responses, a post-hoc analysis of two clinic
Complete information for FAF2 gene (Protein Coding), Fas Associated Factor Family Member 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Alain Frisch wrote: , , On Tue, 29 May 2001, Tore Lund wrote: , , , Sorry, doesnt work. I try to compile the following file: , , , , let _ = c_test ();; , , , , and all I get is this: , , , , C:\Data\ocaml,ocamlc -use-prims prims ctest.ml , , File "ctest.ml", line 1, characters 8-14: , , Unbound value c_test , , , , even though I have put c_test at the bottom of the list in prims. , , , , Any ideas? , , You have to declare the primitive to Caml: , , external c_test: unit -, unit = "c_test" Thanks, I just found out myself. -- Tore ------------------- To unsubscribe, mail [email protected] Archives: http://caml.inria.fr ...
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Looking for online definition of heat-shock transcription factor family member 5 in the Medical Dictionary? heat-shock transcription factor family member 5 explanation free. What is heat-shock transcription factor family member 5? Meaning of heat-shock transcription factor family member 5 medical term. What does heat-shock transcription factor family member 5 mean?
Professor Fabienne Mackay obtained her PhD from Louis Pasteur University, Strasbourg, France. She is Inaugural Head, School of Biomedical Sciences. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia. Her laboratory helped the BAFF inhibitor approved by the FDA in 2011: first new treatment for lupus in over 50 years. first new treatment for lupus in over 50 years. Prof Mackays group is focusing on inhibitors for the BAFF receptor TACI to treat Systemic Lupus Erythematosus and Chronic Lymphocytic Leukaemia without compromising key immune function and, therefore, an approach that has a better safety profile. Her research and teaching directly influence clinical practice and continues to make internationally significant contributions to the field of autoimmunity and oncology, with a strong record of knowledge translation and community engagement. She is a Council Member, International Cytokine & Interferon Society and Fellow, Australian Academy of Health and ...
Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response.
Overall, grade 3 or higher IRAEs developed in 10 of 23 patients following combination therapy, in 1 of 8 patients following anti-CTLA4 therapy, and in 1 of 8 patients following anti-PD1 therapy. The finding that CCB leads to higher rates of IRAEs as well as significant and distinct changes in B cells, including a decline in circulating B cells as well as an increase in CD21lo B cells and plasmablasts, led us to evaluate the correlation between these changes and the development of autoimmunity. Interestingly, the severity of an early decline in B cell numbers after therapy directly correlated with the time to onset of toxicity (Figure 3B; P = 0.007) as well as the grade of maximal toxicity (Figure 3C). The ability to identify patients at increased risk for developing autoimmunity is critical for the application of CCB. We developed a parameter for B cell changes following combination therapy by integrating the decline in B cell numbers (fold change after therapy, ≤70% of baseline) with a 2-fold ...
Overall, grade 3 or higher IRAEs developed in 10 of 23 patients following combination therapy, in 1 of 8 patients following anti-CTLA4 therapy, and in 1 of 8 patients following anti-PD1 therapy. The finding that CCB leads to higher rates of IRAEs as well as significant and distinct changes in B cells, including a decline in circulating B cells as well as an increase in CD21lo B cells and plasmablasts, led us to evaluate the correlation between these changes and the development of autoimmunity. Interestingly, the severity of an early decline in B cell numbers after therapy directly correlated with the time to onset of toxicity (Figure 3B; P = 0.007) as well as the grade of maximal toxicity (Figure 3C). The ability to identify patients at increased risk for developing autoimmunity is critical for the application of CCB. We developed a parameter for B cell changes following combination therapy by integrating the decline in B cell numbers (fold change after therapy, ≤70% of baseline) with a 2-fold ...
Overall, grade 3 or higher IRAEs developed in 10 of 23 patients following combination therapy, in 1 of 8 patients following anti-CTLA4 therapy, and in 1 of 8 patients following anti-PD1 therapy. The finding that CCB leads to higher rates of IRAEs as well as significant and distinct changes in B cells, including a decline in circulating B cells as well as an increase in CD21lo B cells and plasmablasts, led us to evaluate the correlation between these changes and the development of autoimmunity. Interestingly, the severity of an early decline in B cell numbers after therapy directly correlated with the time to onset of toxicity (Figure 3B; P = 0.007) as well as the grade of maximal toxicity (Figure 3C). The ability to identify patients at increased risk for developing autoimmunity is critical for the application of CCB. We developed a parameter for B cell changes following combination therapy by integrating the decline in B cell numbers (fold change after therapy, ≤70% of baseline) with a 2-fold ...
In this study, we sought to address changes in blood lymphocyte subpopulations and labial salivary gland (LSG) inflammation after belimumab treatment in patients with primary Sjögrens syndrome (pSS) and to identify predictors of response to treatment. Sequential blood lymphocyte subsets and LSG biopsies were analysed between week 0 (W0) and W28 in 15 patients with pSS treated with belimumab. Systemic response to treatment was defined as a decrease in the European League Against Rheumatism Sjögrens Syndrome Disease Activity Index score of ≥3 points at W28. After belimumab, we observed a decrease in blood B lymphocytes primarily involving CD27-negative/immunoglobulin D-positive naïve B cells (p=0.008). Lymphocytic sialadenitis (focus score |1) that was present in 12 patients (80.0 %) before belimumab treatment became negative in 5 of them after treatment (p=0.03). The median (interquartile range) LSG B-cell/T-cell ratio decreased from 0.58 (0.5-0.67) to 0.50 (0.5-0.5) (p=0.06). B-cell activating
SPPL2A-mediated processing of CD74 is essential for B cell development (11) and B cell receptor signaling in transitional B cells (14). CD74 binds to MHCII dimers in the ER of antigen-presenting cells and prevents premature peptide binding. Upon the proteolytic processing of CD74, MHCII is released. Impaired processing of CD74 leads to impaired Ag presentation by MHCII (22). CD74 also functions in the endocytic trafficking and endosomal maturation of antigen presenting cells (23;24). Dendritic cell migration (25) and the function of the proinflammatory cytokine macrophage migration inhibitory factor (26) are also CD74-dependent.. Sppl2a knockout (Sppl2a-/-) mice have a B cell developmental block during the splenic phase of B cell maturation. As a result, the frequency of mature and functionally competent B cells is reduced and the mice exhibit impaired humoral immune responses (11). In Sppl2a-deficient B cells, accumulation of the CD74 N-terminal fragment results in B cell maturation arrest at ...

Novel evidence-based systemic lupus erythematosus responder index - Furie - 2009 - Arthritis Care & Research - Wiley Online...Novel evidence-based systemic lupus erythematosus responder index - Furie - 2009 - Arthritis Care & Research - Wiley Online...

William Stohl, The Future of B-cell Activating Factor Antagonists in the Treatment of Systemic Lupus Erythematosus, Journal of ... William Stohl, Inhibition of B cell activating factor (BAFF) in the management of systemic lupus erythematosus (SLE), Expert ...
more infohttp://onlinelibrary.wiley.com/doi/10.1002/art.24698/abstract

B-cell activating factor - WikipediaB-cell activating factor - Wikipedia

B-cell activating factor (BAFF) also known as tumor necrosis factor ligand superfamily member 13B is a protein that in humans ... "Elevated B cell-activating factor of the tumour necrosis factor family in coeliac disease". Scandinavian Journal of ... B-Cell Activating Factor at the US National Library of Medicine Medical Subject Headings (MeSH) Human DTL genome location and ... PMC 3723786 . Lied GA, Lillestøl K, Valeur J, Berstad A (July 2010). "Intestinal B cell-activating factor: an indicator of non- ...
more infohttps://en.wikipedia.org/wiki/B-cell_activating_factor

BAFF // B Cell Activating Factor | BioclinicaBAFF // B Cell Activating Factor | Bioclinica

... is a member of the TNF family and induces B cell proliferation and differentiation. The soluble form of BAFF is a 152aa with a ... single disulfide bond (Moore et al., 1999). This cytokine is also called tumor necrosis factor ligand superfamily member 13b ( ... B-cell Activating Factor (BAFF) is a member of the TNF family and induces B cell proliferation and differentiation. The soluble ... BAFF is one of the major factors implicated in the maturation and survival of B cells (Cancro, 2004). Mice overexpressing BAFF ...
more infohttp://bioclinica.com/biomarker-services/biomarker-menu/baff-b-cell-activating-factor

B-Cell Activating Factor (BAFF) Inhibitors - Pipeline Insights, 2017B-Cell Activating Factor (BAFF) Inhibitors - Pipeline Insights, 2017

B-Cell Activating Factor (BAFF) Inhibitors Overview. B-Cell Activating Factor (BAFF) Inhibitors Disease Associated. B-Cell ... B-Cell Activating Factor (BAFF) Inhibitors Phase I and IND Filed Products. Comparative Analysis. B-Cell Activating Factor (BAFF ... B-Cell Activating Factor (BAFF) Inhibitors Filed and Phase III Products. Comparative Analysis. B-Cell Activating Factor (BAFF) ... B-Cell Activating Factor (BAFF) Inhibitors Assessment by Stage and Route of Administration. B-Cell Activating Factor (BAFF) ...
more infohttps://www.researchandmarkets.com/reports/4036909/b-cell-activating-factor-baff-inhibitors

B-cell activating factor (BAFF) promotes CpG ODN-induced B cell activation and proliferation.  - PubMed - NCBIB-cell activating factor (BAFF) promotes CpG ODN-induced B cell activation and proliferation. - PubMed - NCBI

Cell Immunol. 2011;271(1):16-28. doi: 10.1016/j.cellimm.2011.05.016. Epub 2011 Jun 14. Research Support, Non-U.S. Govt ... myeloid cells and/or B-cell activating factor (BAFF), a cytokine produced by activated myeloid cells, there was a significant ... B-cell activating factor (BAFF) promotes CpG ODN-induced B cell activation and proliferation.. Buchanan RM1, Popowych Y, Arsic ... all of which are markers for B cell activation. These data suggest that activated myeloid cells and BAFF prime B cells for ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/21724179?dopt=Abstract

B-cell activating factor (BAFF) - keep the level steady! | Antibody News: Novus BiologicalsB-cell activating factor (BAFF) - keep the level steady! | Antibody News: Novus Biologicals

... and its downstream signaling plays a critical role in B-cell survival and maturation. ... BAFF belongs to the tumor necrosis factor (TNF) family, ... B-cell activating factor (BAFF) - keep the level steady!. Wed, ... Home » Antibody News » B-cell activating factor (BAFF) - keep the level steady! ... BAFF belongs to the tumor necrosis factor (TNF) family, and its downstream signaling plays a critical role in B-cell survival ...
more infohttps://www.novusbio.com/antibody-news/antibodies/b-cell-activating-factor-baff-keep-the-level-steady

B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans | PNASB-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans | PNAS

2001) Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family ... B cell-activating factor belonging to the TNF family acts through separate receptors to support B cell survival and T cell- ... B-cell survival depends on signals induced by B-cell activating factor (BAFF) binding to its receptor (BAFF-R). In mice, ... 2004) TNF family member B cell-activating factor (BAFF) receptor-dependent and -independent roles for BAFF in B cell physiology ...
more infohttps://www.pnas.org/content/106/33/13945

B-Cell-Activating Factor Affects the Occurrence of Thyroid Autoimmunity in Chronic Hepatitis C Patients Treated with Interferon...B-Cell-Activating Factor Affects the Occurrence of Thyroid Autoimmunity in Chronic Hepatitis C Patients Treated with Interferon...

B-Cell-Activating Factor Affects the Occurrence of Thyroid Autoimmunity in Chronic Hepatitis C Patients Treated with Interferon ... P. Schneider, F. Mackay, V. Steiner et al., "BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth ... S. L. Kalled, C. Ambrose, and Y. M. Hsu, "BAFF: B cell survival factor and emerging therapeutic target for autoimmune disorders ... a TNF homologue that activates apoptosis, nuclear factor-κB, and c-jun NH," Journal of Biological Chemistry, vol. 274, no. 23, ...
more infohttps://www.hindawi.com/journals/jir/2012/247973/ref/

A Functional Receptor for B-Cell-Activating Factor Is Expressed on Human Acute Lymphoblastic Leukemias | Cancer ResearchA Functional Receptor for B-Cell-Activating Factor Is Expressed on Human Acute Lymphoblastic Leukemias | Cancer Research

BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative ... indicating an urgent need to better understand the factors that promote their survival. B-cell-activating factor (BAFF) and its ... and multiple myeloma express abnormal levels of B-cell-activating factor (BAFF), which protects these cells from spontaneous or ... Transcription factor NF-κB is constitutively activated in acute lymphoblastic leukemia cells. Leukemia 2000;14:399-402. ...
more infohttp://cancerres.aacrjournals.org/content/70/11/4346

B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic...B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic...

B-cell activating factor, BAFF) developed CD5+ B-cell leukemia resembling human chronic lymphocytic leukemia (CLL), which also ... B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic ... B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic ... B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic ...
more infohttps://www.pnas.org/content/early/2010/10/12/1013420107?elq=a8ed40aa038c4214b873c5894deed0df

PRIME PubMed | Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with Interstitial...PRIME PubMed | Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with Interstitial...

PubMed journal article Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with ... B-Cell Activating FactorBiomarkersCase-Control StudiesChildChild, PreschoolComorbidityDermatomyositisDisease ProgressionFemale ... Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with Interstitial Lung Disease in ... "Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated With Interstitial Lung Disease in ...
more infohttps://www.unboundmedicine.com/medline/citation/26472413/Increased_Serum_B_Cell_Activating_Factor_and_a_Proliferation_inducing_Ligand_Are_Associated_with_Interstitial_Lung_Disease_in_Patients_with_Juvenile_Dermatomyositis_

Increased serum levels of B-cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies |...Increased serum levels of B-cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies |...

Objective: To investigate serum levels of B-cell activating factor (BAFF) in patients with myositis and correlate these to ... Increased serum levels of B-cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies ... Increased serum levels of B-cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies ...
more infohttp://ard.bmj.com/content/early/2008/07/15/ard.2008.091405

AB0554 Expression of Serum B Cell Activating Factor from the Tumour Necrosis Factor Family (BAFF) and A Proliferation-Inducing...AB0554 Expression of Serum B Cell Activating Factor from the Tumour Necrosis Factor Family (BAFF) and A Proliferation-Inducing...

AB0554 Expression of Serum B Cell Activating Factor from the Tumour Necrosis Factor Family (BAFF) and A Proliferation-Inducing ... AB0554 Expression of Serum B Cell Activating Factor from the Tumour Necrosis Factor Family (BAFF) and A Proliferation-Inducing ... We considered SLE-related factors: disease duration, clinical features, SLE Disease Activity Index (SLEDAI 2K), Systemic Lupus ... B cells were detected by flow cytometry. Statistical analysis has been performed with STATISTICA program, version 8.0. ...
more infohttp://ard.bmj.com/content/73/Suppl_2/989.1

Role of B-Cell-Activating Factor in Adhesion and Growth of Human Multiple Myeloma Cells in the Bone Marrow Microenvironment |...Role of B-Cell-Activating Factor in Adhesion and Growth of Human Multiple Myeloma Cells in the Bone Marrow Microenvironment |...

Cell, Tumor, and Stem Cell Biology Role of B-Cell-Activating Factor in Adhesion and Growth of Human Multiple Myeloma Cells in ... Role of B-Cell-Activating Factor in Adhesion and Growth of Human Multiple Myeloma Cells in the Bone Marrow Microenvironment ... Role of B-Cell-Activating Factor in Adhesion and Growth of Human Multiple Myeloma Cells in the Bone Marrow Microenvironment ... Role of B-Cell-Activating Factor in Adhesion and Growth of Human Multiple Myeloma Cells in the Bone Marrow Microenvironment ...
more infohttp://cancerres.aacrjournals.org/content/66/13/6675?ijkey=a993771b03b03e99d93f01cca5fef0bf7cae2650&keytype2=tf_ipsecsha

Gender-Specific Mechanisms Underlying the Amelioration of High-Fat Diet-Induced Glucose Intolerance in B-Cell-Activating Factor...Gender-Specific Mechanisms Underlying the Amelioration of High-Fat Diet-Induced Glucose Intolerance in B-Cell-Activating Factor...

It has recently been found that B cell activating factor (BAFF) plays an important role in the regulation of energy homeostasis ... Gender-Specific Mechanisms Underlying the Amelioration of High-Fat Diet-Induced Glucose Intolerance in B-Cell-Activating Factor ... and suggest that gender difference should be considered as an important factor in the use of BAFF blockade as a therapeutic ...
more infohttps://www.physiciansweekly.com/gender-specific-mechanisms-underlying-the-amelioration-of-high-fat-diet-induced-glucose-intolerance-in-b-cell-activating-factor-deficient-mice/

Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is...Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is...

The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an ... leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice ... This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent ... They display a developmental block of B cell maturation in the periphery, ...
more infohttps://infoscience.epfl.ch/record/115145

B cell-activating factor belonging to the TNF family acts through separate receptors to support B cell survival and T cell...B cell-activating factor belonging to the TNF family acts through separate receptors to support B cell survival and T cell...

BAFF-R-null mice exhibit loss of mature B cells similar to that observed in BAFF(-/-) and A/WySnJ mice. Also, mice lacking both ... BAFF-R-null mice exhibit loss of mature B cells similar to that observed in BAFF(-/-) and A/WySnJ mice. Also, mice lacking both ... However, while BAFF-R-null mice cannot carry out T cell-dependent Ab formation, they differ from BAFF-deficient mice in ... However, while BAFF-R-null mice cannot carry out T cell-dependent Ab formation, they differ from BAFF-deficient mice in ...
more infohttps://www.garvan.org.au/research/publications/1848

New ELISA for B Cell-Activating Factor | Clinical ChemistryNew ELISA for B Cell-Activating Factor | Clinical Chemistry

B cell-activating factor; APRIL, proliferation-inducing ligand; SF, synovial fluid; RF, rheumatoid factor; mAb, monoclonal ... New ELISA for B Cell-Activating Factor. Laëtitia Le Pottier, Boutahar Bendaoud, Yves Renaudineau, Pierre Youinou, Jacques- ... New ELISA for B Cell-Activating Factor. Laëtitia Le Pottier, Boutahar Bendaoud, Yves Renaudineau, Pierre Youinou, Jacques- ... New ELISA for B Cell-Activating Factor. Laëtitia Le Pottier, Boutahar Bendaoud, Yves Renaudineau, Pierre Youinou, Jacques- ...
more infohttp://clinchem.aaccjnls.org/content/55/10/1843

Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis.  - PubMed - NCBICarcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. - PubMed - NCBI

Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis.. Kim S1, Takahashi H, Lin WW, ... By activating TLR2:TLR6 complexes and inducing TNF-alpha secretion by myeloid cells, versican strongly enhances LLC metastatic ... A. WT and Tlr2−/− lungs were analyzed 9 days after inoculation of DsRed-LLC (2×105 cells) for DsRed and myeloid cells markers ( ... we conducted a biochemical screen for macrophage-activating factors secreted by metastatic carcinomas. Here we show that, among ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/19122641?dopt=Abstract

Nuclear factor of activated T cells 2a - Xiphophorus maculatus (Southern platyfish)Nuclear factor of activated T cells 2a - Xiphophorus maculatus (Southern platyfish)

Nuclear factor of activated T cells 2aImported. ,p>Information which has been imported from another database using automatic ... tr,M3ZP49,M3ZP49_XIPMA Nuclear factor of activated T cells 2a OS=Xiphophorus maculatus OX=8083 PE=4 SV=2 ... Nuclear factor of activated T cells.... Nuclear factor of activated T cells 2a ... Nuclear factor of activated T cells 2a. sailfin molly. 882. Nuclear factor of activated T cells 2a. Poecilia mexicana ...
more infohttps://www.uniprot.org/uniprot/M3ZP49

A novel T cell activating factor - UBC Library Open CollectionsA novel T cell activating factor - UBC Library Open Collections

Garman and Raulet described a T cell-activating factor present in the supernatant of ConA activated murine spleen cells (41). ... A novel T cell activating factor Williams, Laura Dawn 1987 pdf. Your browser doesnt seem to have a PDF viewer, please download ... A NOVEL T CELL ACTIVATING FACTOR By LAURA DAWN WILLIAMS B.S c , The Un i v e r s i t y of B r i t i s h Columbia, 1985 A THESIS ... The most studied factor is T cell growth factor (TCGF) which is also termed interleukin-2 (IL-2). This lymphokine is produced ...
more infohttps://open.library.ubc.ca/cIRcle/collections/ubctheses/831/items/1.0097226

B-cell maturation antigen, a proliferation-inducing ligand, and B-cell activating factor are candidate mediators of spinal cord...B-cell maturation antigen, a proliferation-inducing ligand, and B-cell activating factor are candidate mediators of spinal cord...

... and B-cell-activating factor (BAFF), and one receptor, B-cell maturation antigen (BMCA) involved in B cell development, ... To our knowledge, this is the first report that peripheral blood mononuclear cells produce increased levels of BAFF and APRIL ... This finding provides evidence of systemic regulation of SCI-autoimmunity via APRIL and BAFF mediated activation of B cells ... Recent groundbreaking studies in rodents indicate that B cells are responsible for SCI-induced autoimmunity. This novel ...
more infohttps://www.semanticscholar.org/paper/B-cell-maturation-antigen%2C-a-proliferation-inducing-Saltzman-Battaglino/48400ebb149b18a4f2266323edcfb4a65da4772d

Rezeptoren für B cell Activating Factor of the Tumor Necrosis Factor Family (BAFF) auf Synovialen Fibroblasten - Vergleichende...Rezeptoren für B cell Activating Factor of the Tumor Necrosis Factor Family (BAFF) auf Synovialen Fibroblasten - Vergleichende...

Rezeptoren für B cell Activating Factor of the Tumor Necrosis Factor Family (BAFF) auf Synovialen Fibroblasten - Vergleichende ... Anssar, Tareq Marius (2016) Rezeptoren für B cell Activating Factor of the Tumor Necrosis Factor Family (BAFF) auf Synovialen ... Finally, taking into account BAFF function in other cell types, SF were stimulated with BAFF and stained with Annexin V in ... In a further step, the influence of several stimulants, including cytokines, TLR-agonists and cell activators on receptor ...
more infohttps://epub.uni-regensburg.de/34504/

Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. | The Journal of ImmunologyCross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. | The Journal of Immunology

Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B.. I Berberich, G L Shu and E A Clark ... NF-kappa B-like transcription factors are activated after cross-linking CD40 on resting human tonsillar B cells and on B cell ... Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. ... Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. ...
more infohttps://www.jimmunol.org/content/153/10/4357?ijkey=bba76703a5316d9b056653a043e555e64ea92e38&keytype2=tf_ipsecsha

RCSB PDB - Protein Feature View 









 - Nuclear factor of activated T-cells, cytoplasmic 1 - O95644 (NFAC1 HUMAN)RCSB PDB - Protein Feature View - Nuclear factor of activated T-cells, cytoplasmic 1 - O95644 (NFAC1 HUMAN)

Other members such as NFATC4, NFATC3 or members of the activating protein-1 family, MAF, GATA4 and Cbp/p300 can also bind the ... Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 or IL-4 gene ... Also controls gene expression in embryonic cardiac cells. Could regulate not only the activation and proliferation but also the ... differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells (PubMed:10358178). Required ...
more infohttps://www.rcsb.org/pdb/protein/O95644
  • Leukemia cells harvested from spleens were plated on irradiated OP9 feeder layers and grown in αMEM (Life Technologies), 20% fetal bovine serum (FBS), 1% l -glutamine, and 1% penicillin/streptomycin. (aacrjournals.org)
  • Although this group may include a few cases of BTK deficiency ( 12 ), most B-lymphopenic patients have unknown defects, some of which may affect genes regulating early B-cell development and/or B-cell survival ( 13 ). (pnas.org)
  • Our results define the NF-kappa B system as an intermediate event in CD40 signaling and suggest that the CD40 pathway can influence the expression of B cell-associated genes with NF-kappa B consensus sites. (jimmunol.org)
  • Due to the binding of NFATc1 and NFATc2 to the promoters of the gamma interferon (IFN-γ), IL-4, and IL-5 genes (i.e., the promoters of genes that are active either in Th1 or in Th2 cells), it has been assumed that NFATc1 and NFATc2 play an important role in driving naive T cells to effector Th1 and Th2 cells. (asm.org)
  • Previously, we and others have shown that stroma exerts a protective effect that contributes to the poor response of leukemic cells to chemotherapeutic drugs ( 9 - 11 ), and the examination of the molecular nature of the protection provided by stroma remains the focus of significant interest. (aacrjournals.org)
  • They are crucial for the regulation of other cells, the maintenance of a proinflammatory environment and bone destruction. (uni-regensburg.de)
  • Metastatic progression depends on genetic alterations intrinsic to cancer cells as well as the inflammatory microenvironment of advanced tumours. (nih.gov)
  • Primary viably frozen human ALL cells were engrafted through tail vein injections into female NOD.Cg- Prkdc scid Il2rg tm1Wjll /SzJ mice (The Jackson Laboratory). (aacrjournals.org)
  • D. Lungs of WT and Tnfα −/− mice 47 days after LLC inoculation (2×10 5 cells). (nih.gov)
  • D. RNA was extracted from lungs of WT or Tlr2 −/− mice at indicated times after LLC inoculation (2×10 5 cells). (nih.gov)
  • While IL-4, IL-5, and IL-13 mRNA expression was also enhanced in lymph node cells from the lungs of infected NFATc2 −/− mice, the number of T cells secreting Th2-type lymphokines remained the same in mice infected with N. brasiliensis . (asm.org)
  • Figure 1 shows that prior to infection, T cells from the mediastinal lymph nodes (MLN), mesenteric lymph nodes (MESLN), and spleens of both types of mice secreted no or only very low amounts of IL-4 and IL-5 after in vitro stimulation with anti-CD3 (α-CD3) antibodies (Abs) and IL-2 (for descriptions of cell preparations and enzyme-linked immunosorbent assays [ELISAs], see reference 2 ). (asm.org)
  • To understand how cancer cells affect the inflammatory microenvironment, we conducted a biochemical screen for macrophage-activating factors secreted by metastatic carcinomas. (nih.gov)
  • Searching for genetic defects affecting B-cell homeostasis, we screened a cohort of 138 CVID patients for individuals with low numbers of peripheral B cells. (pnas.org)
  • However, the detailed inhibitory mechanisms at the molecular level of CAPE on T-cell activation are still unknown. (aspetjournals.org)
  • Pyrroloquinoline quinone (PQQ), a redox cofactor for bacterial dehydrogenases, has been implicated to be an important nutrient in mammals functioning as a potent growth factor. (sigmaaldrich.com)