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.Immunoglobulin kappa-Chains: One of the types of light chains of the immunoglobulins with a molecular weight of approximately 22 kDa.Immunoglobulin lambda-Chains: One of the types of light chain subunits of the immunoglobulins with a molecular weight of approximately 22 kDa.Genes, Immunoglobulin Light Chain: Genes and gene segments encoding the IMMUNOGLOBULIN LIGHT CHAINS. Gene segments of the light chain genes are designated as V (variable), J (joining), and C (constant).Amyloidosis: A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.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.Bence Jones Protein: An abnormal protein with unusual thermosolubility characteristics that is found in the urine of patients with MULTIPLE MYELOMA.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.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).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.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)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.Myeloma Proteins: Abnormal immunoglobulins characteristic of MULTIPLE MYELOMA.Immunoglobulin 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.Plasmacytoma: Any discrete, presumably solitary, mass of neoplastic PLASMA CELLS either in BONE MARROW or various extramedullary sites.Amyloid: A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.Myosin Light Chains: The smaller subunits of MYOSINS that bind near the head groups of MYOSIN HEAVY CHAINS. The myosin light chains have a molecular weight of about 20 KDa and there are usually one essential and one regulatory pair of light chains associated with each heavy chain. Many myosin light chains that bind calcium are considered "calmodulin-like" proteins.Sharks: A group of elongate elasmobranchs. Sharks are mostly marine fish, with certain species large and voracious.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 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.Light: That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range.Multiple Myeloma: A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.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.Paraproteinemias: A group of related diseases characterized by an unbalanced or disproportionate proliferation of immunoglobulin-producing cells, usually from a single clone. These cells frequently secrete a structurally homogeneous immunoglobulin (M-component) and/or an abnormal immunoglobulin.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.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.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.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.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.Pseudolymphoma: A group of disorders having a benign course but exhibiting clinical and histological features suggestive of malignant lymphoma. Pseudolymphoma is characterized by a benign infiltration of lymphoid cells or histiocytes which microscopically resembles a malignant lymphoma. (From Dorland, 28th ed & Stedman, 26th ed)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.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: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Receptors, Antigen, B-Cell: IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.Immunoglobulin Fragments: Partial immunoglobulin molecules resulting from selective cleavage by proteolytic enzymes or generated through PROTEIN ENGINEERING techniques.Waldenstrom Macroglobulinemia: A lymphoproliferative disorder characterized by pleomorphic B-LYMPHOCYTES including PLASMA CELLS, with increased levels of monoclonal serum IMMUNOGLOBULIN M. There is lymphoplasmacytic cells infiltration into bone marrow and often other tissues, also known as lymphoplasmacytic lymphoma. Clinical features include ANEMIA; HEMORRHAGES; and hyperviscosity.Fanconi Syndrome: A hereditary or acquired form of generalized dysfunction of the PROXIMAL KIDNEY TUBULE without primary involvement of the KIDNEY GLOMERULUS. It is usually characterized by the tubular wasting of nutrients and salts (GLUCOSE; AMINO ACIDS; PHOSPHATES; and BICARBONATES) resulting in HYPOKALEMIA; ACIDOSIS; HYPERCALCIURIA; and PROTEINURIA.Plasma Cells: Specialized forms of antibody-producing B-LYMPHOCYTES. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses and normally do not circulate in the blood or lymph. (Rosen et al., Dictionary of Immunology, 1989, p169 & Abbas et al., Cellular and Molecular Immunology, 2d ed, p20)Myosin-Light-Chain Kinase: An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.Hypergammaglobulinemia: An excess of GAMMA-GLOBULINS in the serum due to chronic infections or PARAPROTEINEMIAS.Blood Protein Electrophoresis: Electrophoresis applied to BLOOD PROTEINS.Lymphoma, B-Cell: A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.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.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.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).Immunoglobulins, Intravenous: Immunoglobulin preparations used in intravenous infusion, containing primarily IMMUNOGLOBULIN G. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric AIDS; primary HYPERGAMMAGLOBULINEMIA; SCID; CYTOMEGALOVIRUS infections in transplant recipients, LYMPHOCYTIC LEUKEMIA, CHRONIC; Kawasaki syndrome, infection in neonates, and IDIOPATHIC THROMBOCYTOPENIC PURPURA.Nephelometry and Turbidimetry: Chemical analysis based on the phenomenon whereby light, passing through a medium with dispersed particles of a different refractive index from that of the medium, is attenuated in intensity by scattering. In turbidimetry, the intensity of light transmitted through the medium, the unscattered light, is measured. In nephelometry, the intensity of the scattered light is measured, usually, but not necessarily, at right angles to the incident light beam.Prealbumin: A tetrameric protein, molecular weight between 50,000 and 70,000, consisting of 4 equal chains, and migrating on electrophoresis in 3 fractions more mobile than serum albumin. Its concentration ranges from 7 to 33 per cent in the serum, but levels decrease in liver disease.Myosins: A diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind ACTINS and hydrolyze MgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and MgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain.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)Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Peptostreptococcus: A genus of gram-positive, anaerobic, coccoid bacteria that is part of the normal flora of humans. Its organisms are opportunistic pathogens causing bacteremias and soft tissue infections.Kinetics: The rate dynamics in chemical or physical systems.DNA: 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).Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Isoelectric Focusing: Electrophoresis in which a pH gradient is established in a gel medium and proteins migrate until they reach the site (or focus) at which the pH is equal to their isoelectric point.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.Circular Dichroism: A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)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.Nucleic Acid Hybridization: Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)Immunoglobulin E: An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Molecular Weight: The sum of the weight of all the atoms in a molecule.Immunoglobulin A, Secretory: The principle immunoglobulin in exocrine secretions such as milk, respiratory and intestinal mucin, saliva and tears. The complete molecule (around 400 kD) is composed of two four-chain units of IMMUNOGLOBULIN A, one SECRETORY COMPONENT and one J chain (IMMUNOGLOBULIN J-CHAINS).Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.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.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.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Amyloidosis, Familial: Diseases in which there is a familial pattern of AMYLOIDOSIS.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.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.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.Thermodynamics: A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Biological Evolution: The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics.Immunoglobulin D: An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B LYMPHOCYTES.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.Immunoglobulin Fab Fragments: Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Immunoglobulin Fc Fragments: Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Blotting, Southern: A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Kidney Diseases: Pathological processes of the KIDNEY or its component tissues.Immunoglobulin Allotypes: Allelic variants of the immunoglobulin light chains (IMMUNOGLOBULIN LIGHT CHAINS) or heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) encoded by ALLELES of IMMUNOGLOBULIN GENES.Immunoglobulin Class Switching: Gene rearrangement of the B-lymphocyte which results in a substitution in the type of heavy-chain constant region that is expressed. This allows the effector response to change while the antigen binding specificity (variable region) remains the same. The majority of class switching occurs by a DNA recombination event but it also can take place at the level of RNA processing.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.Myosin-Light-Chain Phosphatase: A phosphoprotein phosphatase that is specific for MYOSIN LIGHT CHAINS. It is composed of three subunits, which include a catalytic subunit, a myosin binding subunit, and a third subunit of unknown function.Genetic Code: The meaning ascribed to the BASE SEQUENCE with respect to how it is translated into AMINO ACID SEQUENCE. The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (CODON).

Induction of Ig light chain gene rearrangement in heavy chain-deficient B cells by activated Ras. (1/1652)

During B cell development, rearrangement and expression of Ig heavy chain (HC) genes promote development and expansion of pre-B cells accompanied by the onset of Ig light chain (LC) variable region gene assembly. To elucidate the signaling pathways that control these events, we have tested the ability of activated Ras expression to promote B cell differentiation to the stage of LC gene rearrangement in the absence of Ig HC gene expression. For this purpose, we introduced an activated Ras expression construct into JH-deleted embryonic stem cells that lack the ability to assemble HC variable region genes and assayed differentiation potential by recombination activating gene (RAG) 2-deficient blastocyst complementation. We found that activated Ras expression induces the progression of B lineage cells beyond the developmental checkpoint ordinarily controlled by mu HC. Such Ras/JH-deleted B cells accumulate in the periphery but continue to express markers associated with precursor B cells including RAG gene products. These peripheral Ras/JH-deleted B cell populations show extensive Ig LC gene rearrangement but maintain an extent of kappa LC gene rearrangement and a preference for kappa over lambda LC gene rearrangement similar to that of wild-type B cells. We discuss these findings in the context of potential mechanisms that may regulate Ig LC gene rearrangement.  (+info)

Characterization of an immunoglobin cDNA clone containing the variable and constant regions for the MOPC 21 kappa light chain. (2/1652)

Nucleotide sequence analysis and restriction endonuclease mapping have been used to characterize a cDNA copy of immunoglobulin MOPC 21 Kappa mRNA clones in the bacterial plasmid pMB9. Three regions of the inserted cDNA of plasmid pL21-1 have been sequenced and match the known protein sequence at amino acid residues 1-24, 128-138 and 171-179. With these sequences to provide absolute correlations between the restriction map and the structural gene sequence it has been possible to exactly deduce the positions of all 11 of the insert restriction sites mapped within the structural gene. The pL21-1 insert contains the complete variable and constant regions as well as parts of the 3' untranslated and polypeptide leader coding sequences.  (+info)

Recombinant DNA clones constructed from immunoglobulin kappa light chain messenger RNA. (3/1652)

Recombinant DNA clones have been generated from mouse myeloma MOPC 21 immunoglobulin kappa light chain mRNA. Complementary DNA (cDNA) synthesized on kappa light chain mRNA by reverse transcriptase was made double stranded and inserted into the bacterial plasmid vector, pMB9. Approximately 70 tetracycline-resistant transformed colonies containing kappa light chain mRNA sequences were identified by colony hybridization. Five of these recombinant clones were selected and characterized. Three clones contain both kappa light chain constant and variable region sequences. Two of these three recombinant clones have been shown to include all of the kappa light chain constant and variable region coding sequences. Another of the five selected recombinant clones contain kappa light chain constant region sequences. The remaining characterized clone appears to be derived from sequences at the 5'-end of kappa light chain mRNA, possibly extending to the terminal cap structure.  (+info)

Novel mechanisms control the folding and assembly of lambda5/14.1 and VpreB to produce an intact surrogate light chain. (4/1652)

Surrogate light chain, which escorts the mu heavy chain to the cell surface, is a critical component of the pre-B cell receptor complex. The two proteins that comprise the surrogate light chain, VpreB and lambda5/14.1, contain both unique regions and Ig-like domains. The unique regions have been postulated to function in the assembly of the surrogate light chain. However, by using transient transfection of COS7 cells, we show that deletion of the unique regions of both proteins did not inhibit the assembly of surrogate light chain. Instead, in vivo folding studies showed that the unique region of lambda5/14.1 acts as an intramolecular chaperone by preventing the folding of this protein when it is expressed in the absence of its partner, VpreB. The Ig domains of both lambda5/14.1 and VpreB are atypical. The one in VpreB lacks one of the canonical beta strands whereas the one in lambda5/14.1 has an extra beta strand. Deletion of the extra beta strand in lambda5/14.1 completely abrogated the formation of the surrogate light chain, demonstrating that complementation of the incomplete Ig domain in VpreB by the extra beta strand in lambda5/14.1 was necessary and sufficient for the folding and assembly of these proteins. Our studies reveal two novel mechanisms for regulating surrogate light chain formation: (i) the presence of an intramolecular chaperone that prevents folding of the unassembled subunit but that remains part of the mature assembled protein, and (ii) splitting an Ig domain between two proteins to control their folding and assembly.  (+info)

Assignment of genes for immunoglobulin kappa and heavy chains to chromosomes 6 and 12 in mouse. (5/1652)

Using somatic cell hybrids from fusions of lymphocytes of two different mouse stocks with the myeloma cell line X63-Ag8, we have assigned genes for the immunoglobulin heavy and kappa-type light chains to chromosomes 12 and 6, respectively. The two mouse stocks exhibit karyotypes consisting of nine pairs of metacentric chromosomes as a result of centric fusions of acrocentric chromosomes in different combinations. In the hybrid cells these metacentric chromosomes can be distinguished from the acrocentric chromosomes of myeloma origin, permitting correlation of Ig chain expression with mitotic loss of individual metacentric chromosomes.  (+info)

The structure of an entire noncovalent immunoglobulin kappa light-chain dimer (Bence-Jones protein) reveals a weak and unusual constant domains association. (6/1652)

Monoclonal free light chains secreted in immunoproliferative disorders are frequently involved in renal complications, including a specific proximal tubule impairment, Fanconi's syndrome. The latter is characterized in most cases by intracellular crystallization including a light-chain variable-domain fragment which resists lysosomal proteases. Bence-Jones protein (BJP) DEL was isolated from a patient with myeloma-associated Fanconi's syndrome. The crystal structure of this human kappa immunoglobulin light-chain noncovalent dimer was determined using molecular replacement with the structure of molecule REI, as the variable domain, and that of BJP LOC as the constant domain. To our knowledge, DEL is the first complete kappa BJP structure described to date. The R-factor is 20.7% at 2.8 A resolution. The BJP DEL dimer was compared with other light-chain dimers and with Fab fragments with a kappa light chain. Although the domain-folding pattern was similar, the relative positions of the constant domains differed. BJP DEL showed a noncanonical quaternary structural arrangement which may be attributable to the poor CL-CL affinity and lack of an interchain disulfide bridge, combined with the conformational editing effect of the crystal-packing forces. Our results suggest that, in the absence of a disulfide bridge, most BJP CLs are probably mobile in solution. This may explain their high susceptibility to proteases and the absence of naturally occurring crystals for these dimers. Furthermore, these findings of an unusual quaternary structure of an immunoglobulin light-chain association extend our knowledge about the large and highly diverse structures of the immunoglobulin superfamily.  (+info)

Physicochemical consequences of amino acid variations that contribute to fibril formation by immunoglobulin light chains. (7/1652)

The most common form of systemic amyloidosis originates from antibody light chains. The large number of amino acid variations that distinguish amyloidogenic from nonamyloidogenic light chain proteins has impeded our understanding of the structural basis of light-chain fibril formation. Moreover, even among the subset of human light chains that are amyloidogenic, many primary structure differences are found. We compared the thermodynamic stabilities of two recombinant kappa4 light-chain variable domains (V(L)s) derived from amyloidogenic light chains with a V(L) from a benign light chain. The amyloidogenic V(L)s were significantly less stable than the benign V(L). Furthermore, only the amyloidogenic V(L)s formed fibrils under native conditions in an in vitro fibril formation assay. We used site-directed mutagenesis to examine the consequences of individual amino acid substitutions found in the amyloidogenic V(L)s on stability and fibril formation capability. Both stabilizing and destabilizing mutations were found; however, only destabilizing mutations induced fibril formation in vitro. We found that fibril formation by the benign V(L) could be induced by low concentrations of a denaturant. This indicates that there are no structural or sequence-specific features of the benign V(L) that are incompatible with fibril formation, other than its greater stability. These studies demonstrate that the V(L) beta-domain structure is vulnerable to destabilizing mutations at a number of sites, including complementarity determining regions (CDRs), and that loss of variable domain stability is a major driving force in fibril formation.  (+info)

Cells with clonal light chains are present in peripheral blood at diagnosis and in apheretic stem cell harvests of primary amyloidosis. (8/1652)

In primary systemic amyloidosis, small numbers of bone marrow plasma cells secrete monoclonal light chains that form extracellular fibrils (amyloid) in various organs. Evidence limited to a few cases suggests that rare clonal elements can also be found in the peripheral blood (PB), and this may be relevant in PB stem cell autotransplantation. Since up to 40% of amyloid clones do not synthesize heavy chains, in order to detect tumor cells with high specificity and sensitivity we developed a seminested allele-specific oligonucleotide polymerase chain reaction for tumor light chains. Clone-related sequences were detected in DNA and/or cDNA from the PB cells of eight of 10 patients at diagnosis and from apheretic collections of three of four cases undergoing PB progenitor autotransplantation. Since there are experimental data suggesting that circulating tumor cells may be involved in the growth of the amyloidogenic clone and may be chemoresistant, these findings are relevant to the use of leukapheresis purging strategies for PB progenitor autotransplantation in amyloidosis.  (+info)

  • Previous analyses of a cDNA library generated from synovium of RA patient BC revealed immunoglobulin κ light chain transcripts with extensive somatic mutation, frequent N region addition, and unexpected variation in the lengths of CDR3 regions which form the center of the antigen binding site. (
  • Comparison of Vkappa and Vlambda N-terminal germline consensus sequences with protein Len and 11-1F4-binding phages indicated that this antibody's cross-reactivity with light chains was related to an invariant proline at position(s) 7 and/or 8, bulky hydrophobic residues at positions 11 and 13, and additionally, to the ability to accommodate amino acid diversity at positions 1-4. (
  • Carbohydrate is attached to an Asx residue at position 25, in the first hypervariable region, associated with the sequence triplet Asx-Ser-Ser, which is postulated to be a common recognition site for glycosylation of immunoglobulins. (
  • In this regard, we previously had reported that mAb 11-1F4, generated by immunizing mice with a thermally denatured variable domain (VL) fragment of the human kappa4 Bence Jones protein Len, bound to a non-native conformational epitope located within the N-terminal 18 residues of fibrillar, as well as partially denatured, Ig light chains (O'Nuallain, B., et al. (
  • An internal molecular deletion occurring in a human lambda type immunoglobulin light (L)-chain (Sm lambda) has been defined by sequence analysis. (
  • Only the nonhybridized RNA gave a T1 ribonuclease fingerprint showing oligonucleotides derived from the variable and constant regions of the light chain messenger RNA. (
  • In addition, this fingerprint showed oligonucleotides derived from the untranslated regions of the light chain messenger RNA. (
  • Third, we shuffled the framework 1 (FR1)-FR3 and complementarity determining region 3 (CDR3) regions of the H and kappa chain V segments of the mAB55-derived IgG molecule with the corresponding regions of the monoreactive IgG mAb13. (
  • The mAb55-derived IgG molecule lost polyreactivity when the H chain CDR3, but not the FR1-FR3 region, was replaced by the corresponding region of mAb13, suggesting that within the H chain, the CDR3 provides the major structural correlate for multiple Ag-binding. (
  • This was formally proved by the multiple Ag-binding of the originally monoreactive mAb13-derived IgG molecule grafted with the mAb55-derived H chain CDR3. (
  • Each immunoglobulin molecule consists of two identical heavy chains and two identical light chains. (
  • The development of FLC specific mAbs is difficult because the mAbs must demonstrate specificity for epitopes that are exposed on FLC but hidden on LC bound to whole immunoglobulin. (
  • 2 Total IgG nephelometric assays will include nontumor immunoglobulin, and measurement of either IgG κ or IgG λ may give a more accurate representation of tumor production. (
  • Each B-cell receptor consists of a pair of heavy and light chains. (
  • Light chains in the tubular fluid are absorbed into the proximal tubule epithelium by binding initially to a receptor that consists of megalin and cubilin ( 9 - 12 ). (
  • Sequence analysis of the immunoglobulin antigen receptor of hepatitis C virus-associated non-Hodgkin lymphomas suggests that the malignant cells are derived from the rheumatoid factor-producing cells that occur mainly in type II cryoglobulinemia. (
  • We applied exhaustive amino acid pattern discovery that initially detected patterns within the VH and VK/VL CDR3s before associating these patterns with each other, either within the same chain (intra-association) or across chains (heavy-light inter-association). (
  • In conclusion, we herein demonstrate that CLL stereotyped subsets can now be more accurately defined based on IG gene usage, CDR3 length and pivotal short amino acid patterns or, remarkably, even single residues with a precise offset in both the HC and LC chain CDR3s. (
  • IMGT standardized criteria for statistical analysis of immunoglobulin V-REGION amino acid properties. (
  • Several new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, along with high-dose chemotherapy and autologous haematopoietic stem cell transplantation, have led to rapid and deep suppression of amyloid light chain production in the majority of patients. (
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Amyloidosis - Diagnosis and treatment - Mayo Clinic
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