Background Earlier studies of immunoglobulin gene sequences in patients with allergic diseases using low-throughput Sanger sequencing have limited the analytic depth for characterization of IgE repertoires. more diverse and more mutated (particularly in the biopsy specimens) and Kenpaullone had more evidence of antigen-driven selection compared with those taken outside of the pollen season or from healthy control subjects. Clonal relatedness was observed for IgE between the blood and nasal biopsy specimens. Furthermore in patients with AR, but not healthy control subjects, we found clonal relatedness between IgE and IgG classes. Conclusion This is the first record that exploits next-generation sequencing to determine regional and peripheral bloodstream repertoires in individuals with respiratory sensitive disease. We demonstrate that organic pollen publicity was connected with adjustments in IgE repertoires which were suggestive of ongoing germinal middle reactions. Furthermore, these ...
Find right answers right now! If were all born with the same set of immunoglobulin genes, how is it that we can respond to different antigens? More questions about Science & Mathematics, how
TY - JOUR. T1 - AID is essential for immunoglobulin V gene conversion in a cultured B cell line. AU - Harris, Reuben S.. AU - Sale, Julian E.. AU - Petersen-Mahrt, Svend K.. AU - Neuberger, Michael S.. N1 - Funding Information: We thank Richard Grenfell for assistance with cell sorting, and we thank Gareth Williams and Rupert Beale for the partial AID cDNA clone and the 3′RACE product, respectively. R.S.H. was the recipient of a Burroughs Wellcome Fund Hitchings-Elion fellowship, and S.K.P.M. was the recipient of an EMBO fellowship. This work was supported in part by grants from the Arthritis Research Campaign and the Leukaemia Research Fund.. PY - 2002/3/5. Y1 - 2002/3/5. N2 - Following productive V gene rearrangement, the functional immunoglobulin genes in the B lymphocytes of man and mouse are subjected to two further types of genetic modification. Class-switch recombination, a region-specific but largely nonhomologous recombination process, leads to a change in constant region of the ...
Objectives We have studied the role of lymphoproliferative tumors in the pathogenesis of autoimmune and the origin of the autoantibodies in PNP. Objectives of this study is to understand the characteristics of immunoglobulin genes of the B-cells isolated from the tumor which can produce auto-antibody.. Methods Total RNA of the tumor cells was then isolated and the mRNA was reversely transcribed into cDNA. V-H and V-L genes were amplified and cloned and their sequences were analyzed.. Results 49 V H genes (527 to 577 bp) and 36V(L) genes ( 445 to 454 bp) sequences were cloned from five tumors. All of the IgV(L) were mostly homologous to IGKV4-01 germ-line gene. The frequency of IgV(H) germ-line gene usage in a decreasing order was IGHV3-23 > IGHV3-9 > IGHV4-31 > IGHV4-59. There was more nucleotide changes occurred in complementary determining regions ( CDR) than those in the framework regions (FR) in the V-H and V-L of B cell clones. In both V-H and V-L, the probability (P) that the number of ...
Describes how B-cell immunoglobulin gene rearrangement tests are used, when they are ordered, and what the results of B-cell immunoglobulin gene rearrangement tests might mean
DNA encoding the rat diversity segment (D), joining segment (JH), and constant (C) region mu, gamma 2a, gamma 1, gamma 2b, epsilon and alpha of the Ig heavy chain has been isolated from a cosmid library. Restriction mapping allowed us to identify two gene clusters: D-JH-C mu and C gamma 1-C gamma 2b-C epsilon-C alpha in addition to a single C gamma 2a gene. Analysis of genomic DNA by Southern blotting permitted identification of the C gamma 2c gene and led to the proposal of the following gene order for the rat Ig heavy chain locus: D-JH-C mu-C delta-(C gamma 2c, C gamma 2a)-C gamma 1-C gamma 2b-C epsilon-C alpha. There is striking homology between the rat and mouse Ig heavy chain loci as regards gene order and distance between CH genes. Partial DNA sequencing confirms this homology and shows that exon sequences are more conserved than are intron sequences. One of the most conserved intron regions between rat and mouse is that spanning the Ig heavy chain enhancer (91% homology). However, the
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Human B lymphocytes expressing the CD5 surface antigen (CD5+ B cells) constitute a subset capable of producing polyspecific antibodies recognizing a variety of self antigens. The repertoire of antibodies produced by CD5+ and CD5- B cells is different. However, it is not yet established whether this distribution is reflected in different immunoglobulin variable region gene (IgV) use. Rearrangement of heavy chain IgV (IgVH) genes represents one of the first identifiable stages in the maturation of B cells, and occurs in a developmentally ordered fashion. The repertoire of IgVH gene expression is highly restricted during fetal life but diversifies progressively after birth. A high frequency of VH gene use from the relatively small VHIV gene family has previously been demonstrated in human fetal liver B cells. In the present study, 102 B cell lines established by Epstein-Barr Virus-transformation of separated CD5+ and CD5- cord blood B cells, were examined for the frequency of IgV expression using ...
Conference Paper: A study of clonality of lymphoma of SJL mice using immunoglobulin gene rearrangements and murine leukaemia virus ...
The immunoglobulin heavy-chain (domain. the variable areas of immunoglobulin (Ig) genetics from adjustable (Sixth is v), variety (D), and becoming a member of (M) gene sections during N cell advancement. The recombination of genetics can be firmly managed within the N lymphoid family tree: the Ig heavy-chain (locus are started in lymphoid progenitors adopted by VH-DJH recombination in pro-B cells. The temporary purchase of Sixth is v(G)M recombination can be mainly established by the ease of access of the different Ig gene sections to the Sixth is v(G)M recombinase, which can be managed by multiple epigenetic systems (Jhunjhunwala et al., 2009; Alt and Perlot, 2008). The locus can be made up of the 3 proximal area of 266 kb size consisting of 16 DH, 4 JH, and 8 CH gene sections and of the distal VH gene bunch increasing over a 2.44 Mb area, which contains 195 VH genetics with the largest VH gene family members consisting of 89 VHJ558 genetics (Johnston et al., 2006). VH-DJH recombination at the ...
Immunogenetic analysis of the B cell receptors (BcRs) has been a richly rewarding field for unraveling the pathogenesis of human lymphomas, including CLL. A biased immunoglobulin gene repertoire is seen as evidence for selection of CLL progenitor cells by antigen. Additional corroborative evidence is provided by the differential prognosis of cases with distinct mutational status of the clonotypic BcRs. However, perhaps the strongest immunogenetic evidence for the importance of interactions with microenvironment in driving CLL development and evolution is the existence of subsets of patients with quasi-identical, stereotyped BcRs, collectively accounting for a remarkable one-third of the entire cohort. These observations have been instrumental in shaping the notion that CLL ontogeny is functionally driven and dynamic, rather than a simple stochastic process. From a clinical perspective, ample evidence indicates that immunogenetic information can be used for the biologically and clinically ...
Human B lymphocytes expressing the CD5 surface antigen (CD5+ B cells) constitute a subset capable of producing polyspecific antibodies recognizing a variety of self antigens. The repertoire of antibodies produced by CD5+ and CD5- B cells is different. However, it is not yet established whether this distribution is reflected in different immunoglobulin variable region gene (IgV) use. Rearrangement of heavy chain IgV (IgVH) genes represents one of the first identifiable stages in the maturation of B cells, and occurs in a developmentally ordered fashion. The repertoire of IgVH gene expression is highly restricted during fetal life but diversifies progressively after birth. A high frequency of VH gene use from the relatively small VHIV gene family has previously been demonstrated in human fetal liver B cells. In the present study, 102 B cell lines established by Epstein-Barr Virus-transformation of separated CD5+ and CD5- cord blood B cells, were examined for the frequency of IgV expression using ...
Lower vertebrate species, including Xenopus laevis, exhibit restricted antibody diversity relative to higher vertebrates. We have analyzed more than 180 VH gene-containing recombinant clones from an unamplified spleen cDNA library by selective sequencing of JH and CH positive clones following iterative hybridization screening with family-specific VH probes, 11 unique families of VH genes, each associated with a unique genomic Southern blot hybridization pattern, are described and compared. Considerable variation in the number of hybridizing components detected by each probe is evident. The nucleotide sequence difference between VH families is as great as, if not more than, that reported in other systems, including representatives of the mammalian, avian, and elasmobranch lineages. Some Xenopus Ig gene families encode alternative amino acids at positions that are otherwise invariant or very rarely substituted in known Igs. Furthermore, variations in complementarity determining region sequences ...
LEPIQUE, A. P.; ARMELIN, Hugo Aguirre. Acth regulares fos and jun families expression through transcriptional control but not C-myc in y-1 adrenocortical cells. Anais.. São Paulo: SBBQ, 1997 ...
Which of the following genes involved in the synthesis of immunoglobulins are linked on a single chromosome? A. C gene for gamma chain and C gene for alpha...
A) Why could gene arrangement be detrimental to lymphocyte survival but indispensable for host integrity? b) Explain the roles of promotors, enhancers, and silencers as they pertain to immunoglobulin gene expression.
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Several genes for the variable region of immunoglobulin heavy chains (VH genes) have been isolated from human fetal liver DNA by using a cDNA plasmid probe containing a mouse VH sequence. The detectable VH genes are separated by 12-16 kilobases of DNA, and hybridization experiments show about 23 hybridizing VH genes in DNA of three different individuals. The complete nucleotide sequence of one of these human VH genes shows that it belongs to the human VHIII subgroup. The VH gene appears to contain an intervening sequence (104 bases in length) within a precursor sequence, between residues -4 and -5. The precursor sequence is itself 19 codons in length. The 3 end of the V gene seems to be at codon 93 or 94, and this is followed by the conserved sequences C-A-C-A-G-T-G and G-A-C-A-C-A-A-A-C-C. The presence of these sequences suggests that similar enzymatic mechanisms are involved in the integration of V genes in both heavy and light chains.
We have analyzed several closely related members of the gene family encoding the variable regions of human immunoglobulin kappa light chains (V kappa genes). Two of these genes differ at a single nucleotide out of 940 bases sequenced, and are believed to be alleles of a locus called HK 101. This substitution results in an amino acid replacement in the first complementarity-determining region of the kappa chain. We also compared the structures of two nonallelic human V kappa loci (HK 101 and HK 137) and found a high degree of sequence homology over a region at least 13.5 kb long. This long block of homology indicates that these two loci arose from a recent gene duplication. The DNA sequences of these two nonallelic V kappa genes exhibit a very unusual distribution of nucleotide substitutions. Seven of the ten substitutions found among 940 bases are clustered in a 39 base stretch encoding the first complementarity-determining region and the second framework region of the protein. We suggest that this
TY - JOUR. T1 - NF-HB (BSAP) is a repressor of the murine immunoglobulin heavy-chain 3′α enhancer at early stages of B-cell differentiation. AU - Singh, Mallika. AU - Birshtein, Barbara K.. PY - 1993/6. Y1 - 1993/6. N2 - We have identified a nuclear factor expressed in pro-B-, pre-B-, and B-cell lines that binds to two sites within the murine immunoglobulin heavy-chain (IgH) 3′α enhancer (3′αE). These sites were defined by oligonucleotide competition in an electrophoretic mobility shift assay (EMSA) and methylation interference footprinting. The 3′αE-binding factor is indistinguishable from NF-HB (B-lineage-specific nuclear factor that binds to the IgH gene) and the B-lineage-specific transcription factor BSAP by several criteria, including similar cell type distribution of binding activity, cross-competition of binding sites in EMSA, similar protein size as demonstrated by UV cross-linking, and sequence identity of one of the 3′αE-binding sites with a BSAP-binding site within the ...
Faust, C H.; Moore, J M.; and Heim, I E., Mouse immunoglobulin mu heavy chain mrna of y5781, a high yield myeloma. (1979). Subject Strain Bibliography 1979. 640 ...
Humans; Animals; Amino Acid Sequence; Molecular Sequence Data; Species Specificity; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Genetic Engineering; Tumor Cells, Cultured; *Genes, Immunoglobulin; Antibodies, Monoclonal/*genetics/immunology; Antibody Affinity; Immunoglobulin Heavy Chains/chemistry/*genetics; Immunoglobulin Variable Region/chemistry/*genetics; Leukemia-Lymphoma, Adult T-Cell; Mice/*genetics/immunology; Recombinant Fusion Proteins/*genetics/immunology. ...
title: Immunoglobulin V(H) chain gene analysis of peripheral blood IgM-producing B cells in patients with Kawasaki disease, doi: 10.3349/ymj.2009.50.4.493, category: Article
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 ...
Diversification of the antibody repertoire in mammals results from a series of apparently random somatically propagated gene rearrangement and mutational events. Nevertheless, it is well known that the adult repertoire of antibody specificities is acquired in a developmentally programmed fashion. As previously shown, rearrangement of the gene segments encoding the heavy-chain variable regions (VH) of mouse antibodies is also developmentally ordered: the number of VH gene segments rearranged in B lymphocytes of fetal mice is small but increased progressively after birth. In this report, human fetal B-lineage cells were also shown to rearrange a highly restricted set of VH gene segments. In a sample of heavy-chain transcripts from a 130-day human fetus the most frequently expressed human VH element proved to be closely related to the VH element most frequently expressed in murine fetal B-lineage cells. These observations are important in understanding the development of immunocompetence. ...
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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.
Some aspects of the work of our group on the human and mouse immunoglobulin κ genes are reviewed. The human κ locus contains a large duplication: a 600 kb C κ-proximal copy with 40 V κ genes is found in the close vicinity of a 440 kb C κ-distal copy with 36 very similar, but not identical, V κ genes. The chimpanzee has only the C κ -proximal copy of the locus. The κ locus of the mouse is close to 3.2 Mb in size, of which 3.1 Mb have been cloned in four contigs, leaving three small gaps of together about 90 kb; 140 V κ genes and pseudogenes were localized and sequenced. In parallel to the elucidation of the structure of the κ loci, the mechanisms of the V-J rearrangement, somatic hypermutation and κ gene expression were studied. Various polymorphisms were detected in the human population and a number of haplotypes defined. in addition to the V κ genes within the loci numerous V κ orphons were localized on different chromosomes. Comparing the κ loci of different species allows some ...
TY - JOUR. T1 - The V(H) and C(H) immunoglobulin genes of swine. T2 - Implications for repertoire development. AU - Butler, J. E.. AU - Sun, J.. AU - Kacskovics, I.. AU - Brown, W. R.. AU - Navarro, P.. PY - 1996/11/1. Y1 - 1996/11/1. N2 - Swine have the largest number of IgG subclass genes of all species so far studied but have a single gene for IgA which occurs in two allelic forms that differ in hinge length. Swine also have constant region genes for Cμ and Cε, but lack a gene homologous to that which encodes IgD in rodents and primates, despite the otherwise high degree of sequence similarity of all other swine C (H) genes with those of humans. Swine have , 20 V(H) genes, a single J(H) and perhaps a limited number of D(H) segments. Newborn piglets show preferential V(H) and D(H) usage and may use gene conversion as a mechanism for expanding their antibody repertoire. Despite the close similarity of their Ig gene sequences to humans, swine belong to the group of animals that includes ...
Antibodies are produced by plasma cells, the terminally differentiated descendants of the B-cell lineage. The early stages of B-cell development occur in the bone marrow, where pro-B cells, which are derived from hematopoietic stem cells, undergo rearrangement of the immunoglobulin heavy-chain genes. This process occurs throughout the life of the individual. At the next stage of B-cell differentiation, in pre-B cells, there is rearrangement of the light-chain genes. This allows the expression of the intact immunoglobulin molecule on the cell surface of the B cell. Each B cell and its progeny express only one rearranged immunoglobulin heavy chain and one light chain. When antigen binds to the surface of the B cell, if the appropriate environmental signals are received, the B cell proliferates and differentiates into a memory B cell that can respond more rapidly to future exposures to that antigen or to a plasma cell that secretes high concentrations of antibodies.. ...
Chronic lymphocytic leukemia (CLL) represents the most frequent leukemia in the Western world. During the last decade, there has been tremendous progress in elucidating the pathogenesis of this disease. One of the most interesting features discovered during this search is the fact that the leukemia cells express immunoglobulin (IG) that may or may not have incurred somatic hypermutations of the IG heavy variable (IGHV) genes. The outcome of CLL patients with leukemia cells using an unmutated IGHV gene is inferior to those patients with leukemia cells that carry a mutated one. In addition to the important observations relating the IG mutation status to clinical behavior, the fact that the IG repertoire in CLL is restricted and also uniquely characterized by the existence of closely similar, stereotyped B cell receptors implies a role for antigen(s) in leukemogenesis ...
The intestinal commensal microbiota is required for development of lymphoid tissues and mucosal immunity in vertebrates. However, little is known of the mechani...
Downloadable! An evolutionary model with a finite number of players and with stochastic mutations is analyzed. The expansion and contraction of strategies is linked to their current relative success, but mutuation, perturbing the system from its deterministic evolution, are present as well. The focus is on the long run implications of ongoing mutations, which drastically reduce the set of equilibria. For 2 by 2 symmetric games with two symmetric strict Nash equilibria the risk dominant equilibrium is selected. In particular, if both strategies have equal security levels, the Pareto dominant Nash equilibrium is selected. In particular, if both strategies have equal security levels, the Pareto dominant Nash equilibrium is selected, even though there is another strict Nash equilibrium. Copyright 1993 by The Econometric Society.(This abstract was borrowed from another version of this item.)
Just as in the bottom of an empty shell, a resident is led by imagination, separated from the world in touch with total relaxation at the reach of some sort of structural comfortable sea floor. The natural form concept gives the impression of residing underneath three large boats positioned upside down on the shore or even more tastefully presented through its wooden
Puri, J; Ben, neriah Y.; Givol, D; and Lonai, P, Antibodies to immunoglobulin heavy chain variable regions protect helper cells from specific suicide by radiolabeled antigen. (1980). Subject Strain Bibliography 1980. 1413 ...
TY - JOUR. T1 - Immunoglobulin heavy chain gene analysis in lymphomas. T2 - A multi-center study demonstrating the heterogeneity of performance of polymerase chain reaction assays. AU - Bagg, Adam. AU - Braziel, Rita M.. AU - Arber, Daniel A.. AU - Bijwaard, Karen E.. AU - Chu, Albert Y.. PY - 2002. Y1 - 2002. N2 - Determination of monoclonality through an evaluation of immunoglobulin heavy chain (IgH) gene rearrangements is a commonly performed and useful diagnostic assay. Many laboratories that perform this assay do so by the polymerase chain reaction (PCR). To evaluate current methods for performing IgH gene testing, 19 different Association of Molecular Pathology (AMP) member laboratories analyzed 29 blinded B cell and T cell lymphoid neoplasm samples of extracted DNA and formalin-fixed, paraffin-embedded (FFPE) tissue and were asked to complete a technical questionnaire. From this study, it is clear that Southern blot analysis remains the diagnostic gold standard, with a 100% diagnostic ...
Crews, Stephen Thomas (1983) The Structure of Mammalian Genes: (1) Antibody Heavy Chain Variable Region Genes: Organization, Diversity, and Somatic Mutation. (2) Structure and Transcription of the DNA Encompassing the Origin of Replication of Human Mitochondrial DNA. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/4dgr-za66. https://resolver.caltech.edu/CaltechTHESIS:08302019-152439482 ...
Characterization of the immunoglobulin (Ig) light (L) and heavy (H) chain genes from the Siberiansturgeon, Acipenser baeri, revealed an Ig structure simhar to the IgM elass of mammals. The serumforms of the sturgeon Ig are tetrameric and dimeric.. The sturgeon IgL gene organization is also of the translocon type, with several variable (V)segments followed by some joining (J) segments and the constant (C) exon indicate that theformation of IgL multicluster organisations in teleosts and elasmobranchs are two separateevolutionary events. The sturgeon VL segments all belong to a single family with some 20 members.Light chain variability is generated by random rearrangement of the VL and J segments. The sturgeon IgL is classified as κ like based on homologies of the VL sequence, and similarities of the recombination signal sequence.. The genomic organization of the IgH locus in sturgeon is of the translocon type. withmultiple V gene segments preceeding several D segments, a number of J segments ...
Author Summary Each time a mammalian cell duplicates its genome in preparation for cell division it activates thousands of so called
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These proteins belong to the immunoglobulin gene superfamily. Human PSGs are composed of an immunoglobulin variable-like domain (red circle) and a variable number of constant-like domains (blue circles). As the figure shows, mouse PSGs are built slightly differently. This supports the idea that PSGs evolved separately on the rodent and primate lineages. ...
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Schlissel, Mark S. and Corcoran, Lynn M. and Baltimore, David (1991) Virus-transformed pre-B cells show ordered activation but not inactivation of immunoglobulin gene rearrangement and transcription. Journal of Experimental Medicine, 173 (3). pp. 711-720. ISSN 0022-1007. https://resolver.caltech.edu/CaltechAUTHORS:SCHLjem91 ...
J:29934 Williams R, Lendahl U, Lardelli M, Complementary and combinatorial patterns of Notch gene family expression during early mouse development. Mech Dev. 1995 Nov;53(3):357-68 ...
TY - JOUR. T1 - HSP90α deficiency does not affect immunoglobulin gene hypermutation and class switch but causes enhanced MHC class II antigen presentation. AU - Li, Yingqian. AU - Li, Shuyin. AU - Hoshino, Mari. AU - Ishikawa, Rikiya. AU - Kajiwara, Chiaki. AU - Gao, Xiang. AU - Zhao, Yaofeng. AU - Ishido, Satoshi. AU - Udono, Heiichiro. AU - Wang, Ji Yang. N1 - Copyright: Copyright 2013 Elsevier B.V., All rights reserved.. PY - 2012/12. Y1 - 2012/12. N2 - Heat shock protein 90 (HSP90) is a molecular chaperone required for efficient antigen presentation and cross-presentation. In addition, HSP90 was recently reported to interact with and stabilize the activation-induced cytidine deaminase (AID) and plays a critical role in immunoglobulin gene hypermutation and class switch recombination. In mice and humans, there are two HSP90 isoforms, HSP90α and HSP90β, but the in vivo role of each isoform remains largely unknown. Here we have analyzed humoral immune responses in HSP90α-deficient mice. We ...
TY - JOUR. T1 - Hereditary systemic immunoglobulin light-chain amyloidosis. AU - Benson, Merrill. AU - Liepnieks, Juris J.. AU - Kluve-Beckerman, Barbara. PY - 2015. Y1 - 2015. N2 - Several members of a family died from renal failure as a result of systemic amyloidosis. Extensive studies to detect previously documented gene mutations associated with amyloidosis failed to identify a causative factor. In search of the genetic basis for this syndrome, amyloid fibrils were isolated from renal tissue of a member of the kin who died while on renal dialysis. Amino acid sequencing of isolated amyloid protein identified sequences compatible with the constant region of the immunoglobulin κ light-chain. Isolation and characterization of κ light-chain protein from serum of an affected member of the kindred revealed mutation in the constant region of kκlight-chain, with cysteine replacing serine at amino acid residue 131. This mutation (Ser131Cys) was confirmed by DNA analysis, which identified a ...
In follicular lymphoma, somatic hypermutation of the immunoglobulin heavy chain genes facilitates the identification of different lymphoma cell clones, and the construction of genealogical trees. To analyze the dissemination of lymphoma cells, and the role of the bone marrow for disease progression, we simultaneously analyzed the somatic hypermutation patterns of lymph node and bone marrow specimens of three patients at onset and relapse. Immunoglobulin heavy chain genes were amplified by polymerase chain reaction, cloned and sequenced. Mutational pedigrees were constructed in a hierarchical order. Where direct transition of one mutation pattern into that of successor clones was not feasible, hypothetical predecessor clones were created, and a probability measurement calculation was introduced. Eighty-five sequenced clones were generated. The average mutation rates were 13,45% for the lymph nodes, and 9,78% for the bone marrows. Forty-two hypothetical predecessor clones were introduced into ...
A recombinant chimeric (murine/human) monoclonal antibody (IgG1k) that functions as an immunosuppressive agent, specifically binding to and blocking the interleukin-2 receptor a-chain (IL-2R alpha, also known as CD25 antigen) on the surface of activated T-lymphocytes. It is a 144 kDa glycoprotein obtained from fermentation of an established mouse myeloma cell line genetically engineered to express plasmids containing the human heavy and light chain constant region genes and mouse heavy and light chain variable region genes encoding the RFT5 antibody that binds selectively to the IL-2R alpha.
Full Text - The B7-CD28 gene family plays a key role in regulating cellular immunity and is closely related to tumorigenesis and immune evasion. Here, we explored associations between clinical and immune features and B7-CD28 gene family expression in Gene Expression Omnibus (GEO) datasets representing 1812 diffuse large B-cell lymphoma (DLBCL) patients. This included 414 in the GSE10846 training cohort and 470 and 928 patients in the GSE31312 and GSE117556 validation cohorts, respectively. Four survival-associated genes identified in the GSE10846 cohort by univariate Cox analysis were incorporated into a multivariate analysis, ultimately establishing a three-gene risk signature. Risk scores assigned based on expression of these genes were validated by Kaplan–Meier and multivariable Cox analyses in the remaining datasets and in important clinical subsets. High-risk patients had shorter overall survival and, in some cases, progression-free survival than low-risk patients. Additionally, expression
The immune system generates diversity by using three distinct mechanisms of genetic alteration. V(D)J recombination, CSR, and SHM. Mechanistically, all three processes can be divided into at least three phases: targeting/recognition, DNA cleavage, and repair (18). In all three cases, transcription is thought to play a key role in targeting of a nuclease to the Ig locus. The cleavage step is thought to result in the production of a DNA DSB, though the creation of the DSB might not be the initial event. In V(D)J recombination for instance, the initial event is the nicking of one strand by the RAG recombinase, followed by hairpin formation and resolution into a blunt DSB (24). It is not known whether the CSR nuclease initially inflicts a single or double-strand break but there is some evidence to suggest that the final product of cleavage is a DSB (25). Finally, there is data to indicate that SHM also involves the creation of a DNA DSB, though that may not necessarily be the first step of the ...
HCAK 1, HCAK1, Ig kappa chain C region, IGKC, Immunoglobulin kappa constant, Immunoglobulin kappa constant region, Immunoglobulin kappa light chain, Kappa 1 immunoglobulin light chain, Km, MGC111575, MGC62011, MGC72072, MGC88770, MGC88771, MGC88809.
To determine whether DNA polymerase plays a role in the hypermutation of immunoglobulin variable genes, we examined the frequency and pattern of substitutions in variable VH6 genes from the peripheral blood lymphocytes of three patients with xeroderma pigmentosum variant disease, whose polymerase had genetic defects. The frequency of mutation was normal but the types of base changes were different: there was a decrease in mutations at A and T and a concomitant rise in mutations at G and C. We propose that more than one polymerase contributes to hypermutation and that if one is absent, others compensate. The data indicate that polymerase is involved in generating errors that occur predominantly at A and T and that another polymerase(s) may preferentially generate errors opposite G and C.. ...
TO THE EDITOR:. We thank Ralf Küppers for his interest in our article1 and for his thoughtful commentary.2 We address each of the points he raises below.. First, Küppers claims that, in contrast to what has been demonstrated in mice,3 not all normal human B-cell progenitors undergo concurrent biallelic DHJH rearrangement during B-cell development, and he cites an analysis performed with Southern blot techniques of 26 B-cell lines derived from 3 individuals to support this claim.4 We analyzed publicly available IGH high-throughput sequencing (HTS) data derived from analysis of B-cell genomic DNA from 60 healthy individuals (available at https://clients.adaptivebiotech.com/immuneaccess), and we conclude that the data strongly suggest that a very high fraction of normal human B cells do indeed undergo biallelic DHJH rearrangement. These IGH HTS data were acquired using the same sequencing platform used for our studies.5 A total of 2 604 887 unique IGH nucleotide sequences, comprising productive ...
Depending on whether the nature of the antigen is protein or polysaccharide and the frequency and duration of stimulation by the antigen, an antibody response may exhibit changes in the distribution of IgG subclasses in plasma, and cause increased or diminished levels of one or more IgG subclasses (Meulenbroek et al., 2000). When the serum level of a subclass is below detection levels of the most sensitive techniques (ELISA/RIA), it is considered as a complete deficiency /absence or a total lack (Meulenbroek et al., 2000). Such complete deficiency is rare and is usually due to deletions in chromosome 14 loci. Such a total lack of one or more IgG subclasses due to deletions of the immunoglobulin heavy chain constant region genes is occasionally found in healthy individuals. The fact that these individuals still produce protective antibody titers in the residual immunoglobulin classes or subclasses suggests that the deletion of the isotype(s) occurs by chance and can be compensated adequately ...
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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.
A role of B cells in multiple sclerosis (MS) is well established, but there is limited understanding of their involvement during active disease. Here, we examined cerebrospinal fluid (CSF) and peripheral blood (PB) B cells in treatment-naive patients with MS or high-risk clinically isolated syndrome. Using flow cytometry, we found increased CSF lymphocytes with a disproportionate increase of B cells compared with T cells in patients with gadolinium-enhancing (Gd+) lesions on brain MRI. Ig gene heavy chain variable region (Ig-VH) repertoire sequencing of CSF and PB B cells revealed clonal relationships between intrathecal and peripheral B cell populations, which could be consistent with migration of B cells to and activation in the CNS in active MS ...
A macrophage activator, IL-4 stimulates phagocytic activity and MHC class II gene expression. IL-4 stimulates isotype switching by activating the promoters for Iε, and Iγ1 (the I regions for ε and γ1 heavy chain constant region genes). IL-4 is pivotal in regulating the IgE response: IgG1 and IgE account ∼2% of all antibodies secreted by splenic B cells incubated with LPS; IgG1 accounts for ∼50% and IgE accounts for ∼20% of all antibodies secreted by B cells incubated with LPS and IL-4. IL-4 knockout mice cannot mount an IgE response to parasites. Also, CD4 T cells activated in presence of IL-4 develop into TH2 cells (especially if IL-6 is also present); IL-4 and IL-10 both inhibit T cell differentiation into TH1 cells ...
The role of autoantibodies in the etiology of autoimmune diseases remains unclear. However, an examination of the sequences of these autoantibodies can be informative. Antibody sequences that violate constraints normally imposed during ontogeny and during development point to a failure of regulation. The existence of clonally related sequences indicates that production of these antibodies may frequently be driven by self-antigen. A better understanding of the mechanisms that normally constrain the composition of the antibody repertoire and of the nature of the inciting and/or driving antigens may yield new insights into both the pathogenesis and potential treatment of these crippling diseases.
2008 (English)In: Immunoglobulin gene analysis in chronic lymphocytic leukemia, Milano: Wolters Kluwer Health/Lippincott Williams & Wilkins , 2008, 113-124 p.Chapter in book (Other academic) ...
Specjalista laboratoryjnej genetyki medycznej. Absolwentka Międzywydziałowych Indywidualnych Studiów Matematyczno-Przyrodniczych i Wydziału Biologii Uniwersytetu Warszawskiego (1999), specjalność biologia molekularna. Dyplom doktora nauk medycznych (biologia medyczna) obroniła z wyróżnieniem w Centrum Biostruktury Akademii Medycznej w Warszawie (2004); pracę doktorską przygotowywała w Zakładzie Genetyki Medycznej Instytutu Matki i Dziecka w ramach Studium Medycyny Molekularnej. Uczestniczyła w licznych konferencjach, warsztatach i stażach badawczych (Ontario Cancer Institute w Toronto, CLB w Amsterdamie, INSERM EMI 210 w Paryżu, European School of Medical Genetics w Sestri Levante, Immunoglobulin Gene Analysis in CLL w Salonikach). Prowadziła i kontynuuje badania w projektach Ministerstwa Nauki i Szkolnictwa Wyższego, 6 Programu Ramowego, Narodowego Centrum Nauki oraz Narodowego Centrum Badań i Rozwoju. Wyniki jej prac zostały opublikowane w kilkunastu artykułach o zasięgu ...
Cat #: 21020011. IGK Tube A - 6FAM for ABI Fluorescence Detection. The human immunoglobulin kappa (IGK) light chain locus on the short arm of chromosome 2 (2p11.2) spans 1820 kb. It is made up of 76 variable (Vκ) g.... View Product ...