Genomes and Genes
Gene Symbol: kappa
Description: immunoglobulin kappa chain complex
Alias: kappa, kappa light chain variable region
- Gorman J, van der Stoep N, Monroe R, Cogne M, Davidson L, Alt F. The Ig(kappa) enhancer influences the ratio of Ig(kappa) versus Ig(lambda) B lymphocytes. Immunity. 1996;5:241-52 pubmedWe generated mice harboring germline mutations in which the enhancer element located 9 kb 3' of the immunoglobulin kappa light chain gene (3'E kappa) was replaced either by a single loxP site (3'E kappa delta) or by a neomycin resistance ..
- Ferradini L, Gu H, De Smet A, Rajewsky K, Reynaud C, Weill J. Rearrangement-enhancing element upstream of the mouse immunoglobulin kappa chain J cluster. Science. 1996;271:1416-20 pubmed..This cis-acting recombination-enhancing element affects the rearrangement process without being involved in regulating transcription. ..
- Braun U, Rajewsky K, Pelanda R. Different sensitivity to receptor editing of B cells from mice hemizygous or homozygous for targeted Ig transgenes. Proc Natl Acad Sci U S A. 2000;97:7429-34 pubmed
- Tze L, Schram B, Lam K, Hogquist K, Hippen K, Liu J, et al. Basal immunoglobulin signaling actively maintains developmental stage in immature B cells. PLoS Biol. 2005;3:e82 pubmed..These studies identify a previously unappreciated level of plasticity in the B cell developmental program, and have important implications for our understanding of central tolerance mechanisms. ..
- Pelanda R, Schwers S, Sonoda E, Torres R, Nemazee D, Rajewsky K. Receptor editing in a transgenic mouse model: site, efficiency, and role in B cell tolerance and antibody diversification. Immunity. 1997;7:765-75 pubmed
- Rowland S, Depersis C, Torres R, Pelanda R. Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation. J Exp Med. 2010;207:607-21 pubmed publisher..These results strongly suggest that tonic BCR signaling mediates the differentiation of immature into transitional and mature B cells via activation of Erk, likely through a pathway requiring Ras. ..
- Manis J, Dudley D, Kaylor L, Alt F. IgH class switch recombination to IgG1 in DNA-PKcs-deficient B cells. Immunity. 2002;16:607-17 pubmed..We conclude that DNA-PKcs is required for CSR to most C(H) genes but that CSR to gamma1 occurs via a DNA-PKcs-independent mechanism. ..
- Ramsden D, Gellert M. Formation and resolution of double-strand break intermediates in V(D)J rearrangement. Genes Dev. 1995;9:2409-20 pubmed..Efficient formation of signal junctions may require cell cycle progression, or down-regulation of the recombination machinery. ..
- Rowland S, Leahy K, Halverson R, Torres R, Pelanda R. BAFF receptor signaling aids the differentiation of immature B cells into transitional B cells following tonic BCR signaling. J Immunol. 2010;185:4570-81 pubmed publisher..In summary, our data indicate that BAFFR and tonic BCR signals cooperate to enable nonautoreactive immature B cells to differentiate into transitional B cells and to be positively selected into the naive B cell repertoire. ..
- Casellas R, Nussenzweig A, Wuerffel R, Pelanda R, Reichlin A, Suh H, et al. Ku80 is required for immunoglobulin isotype switching. EMBO J. 1998;17:2404-11 pubmed..To reconstitute the B-cell compartment in Ku80(-/-) mice, pre-rearranged VB1-8 DJH2 (mu i) and V3-83JK2 (kappa i) genes were introduced into the Ku80(-/-) background (Ku80(-/-)mu i/+kappa i/+)...
- Novobrantseva T, Xu S, Tan J, Maruyama M, Schwers S, Pelanda R, et al. Stochastic pairing of Ig heavy and light chains frequently generates B cell antigen receptors that are subject to editing in vivo. Int Immunol. 2005;17:343-50 pubmed..These data thus suggest that about half of the emerging antibody repertoire is negatively selected during B lymphopoiesis due to the likely encoding of autoreactive or non-functional BCRs. ..
- Kalinina O, Doyle Cooper C, Miksanek J, Meng W, Prak E, Weigert M. Alternative mechanisms of receptor editing in autoreactive B cells. Proc Natl Acad Sci U S A. 2011;108:7125-30 pubmed publisher..The editing mechanisms in the case of ?-expressing B cells include L chain allelic inclusion and V(H) replacement. ..
- Liu S, Velez M, Humann J, Rowland S, Conrad F, Halverson R, et al. Receptor editing can lead to allelic inclusion and development of B cells that retain antibodies reacting with high avidity autoantigens. J Immunol. 2005;175:5067-76 pubmed..These dual Ab-expressing autoreactive B cells conceal their autoantibodies within the cell manifesting a superficially tolerant phenotype that can be partially overcome to secrete IgM autoantibodies. ..
- Yan C, Boboila C, Souza E, Franco S, Hickernell T, Murphy M, et al. IgH class switching and translocations use a robust non-classical end-joining pathway. Nature. 2007;449:478-82 pubmed..In the absence of C-NHEJ, this alternative end-joining pathway also frequently joins Igh locus breaks to other chromosomes to generate translocations...
- Martin D, Van Ness B. Initiation and processing of two kappa immunoglobulin germ line transcripts in mouse B cells. Mol Cell Biol. 1990;10:1950-8 pubmedThe splicing patterns and sequences of two processed kappa immunoglobulin germ line mRNAs are presented. A 1.1-kilobase (kb) mRNA appeared to be derived from splicing of the previously characterized 8.4-kb germ line transcript, while a 0...
- CallÃ©n E, Jankovic M, Wong N, Zha S, Chen H, Difilippantonio S, et al. Essential role for DNA-PKcs in DNA double-strand break repair and apoptosis in ATM-deficient lymphocytes. Mol Cell. 2009;34:285-97 pubmed publisher..Our experiments reveal a DNA-PKcs-dependent pathway that regulates DNA repair and activation of p53 in the absence of ATM. ..
- Siminovitch K, Moore M, Durdik J, Selsing E. The human kappa deleting element and the mouse recombining segment share DNA sequence homology. Nucleic Acids Res. 1987;15:2699-705 pubmed..and human DNA probes to identify regions of conserved homology between the human and murine DNA segments, (termed kappa deleting element (kde) and recombining segment (RS) respectively) which are frequently recombined in lambda-..
- Tonge D, Hennam J, Greene A, Lee I, Edge M. Cloning and characterization of 1116NS19.9 heavy and light chain cDNAs and expression of antibody fragments in Escherichia coli. Year Immunol. 1993;7:56-62 pubmed
- George J, Li S, Garrard W. Yeast artificial chromosome contigs reveal that distal variable-region genes reside at least 3 megabases from the joining regions in the murine immunoglobulin kappa locus. Proc Natl Acad Sci U S A. 1995;92:12421-5 pubmedThe immunoglobulin kappa gene locus encodes 95% of the light chains of murine antibody molecules and is thought to contain up to 300 variable (V kappa)-region genes generally considered to comprise 20 families...
- Dosenovic P, von Boehmer L, Escolano A, Jardine J, Freund N, Gitlin A, et al. Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice. Cell. 2015;161:1505-15 pubmed publisher..The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens. ..
- Torres R, Hafen K. A negative regulatory role for Ig-alpha during B cell development. Immunity. 1999;11:527-36 pubmed..These data illustrate a role for Ig-alpha in negatively regulating antigen receptor signaling during B cell development. ..
- Cascalho M, Martin D, Wong J, Lam Q, Wabl M, Wu G. A mouse with a monoclonal primary immunoglobulin repertoire not further diversified by V-gene replacement. Dev Immunol. 1999;7:43-50 pubmed
- Seidman J, Leder A, Edgell M, Polsky F, Tilghman S, Tiemeier D, et al. Multiple related immunoglobulin variable-region genes identified by cloning and sequence analysis. Proc Natl Acad Sci U S A. 1978;75:3881-5 pubmed..at least six EcoRI fragments of mouse DNA that encode variable-region gene sequences closely related to the mouse kappa light chain, MOPC-149...
- Liu Z, George Raizen J, Li S, Meyers K, Chang M, Garrard W. Chromatin structural analyses of the mouse Igkappa gene locus reveal new hypersensitive sites specifying a transcriptional silencer and enhancer. J Biol Chem. 2002;277:32640-9 pubmed..In summary, our results pinpoint the locations of presumptive regulatory elements for future knockout studies to define their functional roles in the native locus. ..
- Srour N, Chemin G, Tinguely A, Ashi M, Oruc Z, PÃ©ron S, et al. A plasma cell differentiation quality control ablates B cell clones with biallelic Ig rearrangements and truncated Ig production. J Exp Med. 2016;213:109-22 pubmed publisher..The TIE checkpoint thus mediates selection of long-lived PCs with limited ER stress supporting high Ig secretion, but with a cost in terms of antigen-independent narrowing of the repertoire. ..
- Apel T, Scherer A, Adachi T, Auch D, Ayane M, Reth M. The ribose 5-phosphate isomerase-encoding gene is located immediately downstream from that encoding murine immunoglobulin kappa. Gene. 1995;156:191-7 pubmedThe immunoglobulin kappa locus (Ig kappa) is active only in the B-lymphocyte cell lineage. By exon-trapping we found a gene situated downstream from the murine Ig kappa locus...
- Goldmit M, Schlissel M, Cedar H, Bergman Y. Differential accessibility at the kappa chain locus plays a role in allelic exclusion. EMBO J. 2002;21:5255-61 pubmed..Using a model system in which rearrangement of the endogenous immunoglobulin kappa locus is prevented, we demonstrate that these epigenetic and chromatin changes actually occur on one allele with a ..
- Hondowicz B, Alexander S, Quinn W, Pagán A, Metzgar M, Cancro M, et al. The role of BLyS/BLyS receptors in anti-chromatin B cell regulation. Int Immunol. 2007;19:465-75 pubmed..These data suggest a novel role for TACI in anti-chromatin B cell homeostasis and differentiation. ..
- Banerjee M, Wiener F, Spira J, Babonits M, Nilsson M, Sumegi J, et al. Mapping of the c-myc, pvt-1 and immunoglobulin kappa genes in relation to the mouse plasmacytoma-associated variant (6;15) translocation breakpoint. EMBO J. 1985;4:3183-8 pubmed..In situ hybridization was performed on the normal and the inverted Rb chromosomes, using myc and kappa probes...
- Shinohara T, Tomizuka K, Takehara S, Yamauchi K, Katoh M, Ohguma A, et al. Stability of transferred human chromosome fragments in cultured cells and in mice. Chromosome Res. 2000;8:713-25 pubmed..Thus, the hCF(SC20), which was relatively stable in both mouse and human cells, may be a promising candidate for development as a gene delivery vector. ..
- Vinocur J, Fesnak A, Liu Y, Charan D, Prak E. Violations of the 12/23 rule at the mouse immunoglobulin kappa locus, including V kappa-V kappa rearrangement. Mol Immunol. 2009;46:2183-9 pubmed publisher..of different genotyping assays, four different kinds of atypical rearrangements were identified at the murine kappa locus: (1) V kappa to V kappa, (2) J kappa to J kappa, (3) V kappa to iRS, a heptameric sequence found in the J ..
- Zocher I, Röschenthaler F, Kirschbaum T, Schäble K, Horlein R, Fleischmann B, et al. Clustered and interspersed gene families in the mouse immunoglobulin kappa locus. Eur J Immunol. 1995;25:3326-31 pubmedAlthough numerous solitary germ-line V kappa genes and two small V kappa contiguously cloned gene regions (contigs) are known, no attempts to systematically elucidate the structure of the kappa locus of the mouse have been reported so ..
- Kilmon M, Rutan J, Clarke S, Vilen B. Low-affinity, Smith antigen-specific B cells are tolerized by dendritic cells and macrophages. J Immunol. 2005;175:37-41 pubmed..Our data define a tolerogenic role for MPhi and DCs in regulating autoreactive B cells during activation of the innate immune system. ..
- Phan T, Green J, Gray E, Xu Y, Cyster J. Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation. Nat Immunol. 2009;10:786-93 pubmed publisher..Thus, we characterize SCS macrophages as specialized antigen-presenting cells functioning at the apex of an antigen transport chain that promotes humoral immunity. ..
- Cocea L, De Smet A, Saghatchian M, Fillatreau S, Ferradini L, Schurmans S, et al. A targeted deletion of a region upstream from the Jkappa cluster impairs kappa chain rearrangement in cis in mice and in the 103/bcl2 cell line. J Exp Med. 1999;189:1443-50 pubmedWe have shown previously that a mutation of the KI-KII site immediately 5' to J(kappa)1 on the mouse immunoglobulin light chain kappa locus reduces the rearrangement level in cis, although it does not affect transcription...
- Ng K, Lavigueur A, Ricard L, Boivrette M, Maclean S, Cloutier D, et al. Characterization of allelic V kappa-1 region genes in inbred strains of mice. J Immunol. 1989;143:638-48 pubmedGerm line genes encoding mouse Ig kappa-chains belonging to the V kappa-1 group have been isolated from BALB/c, NZB, and CE, three inbred strains of differing kappa haplotype...
- Magari M, Sawatari T, Kawano Y, Cascalho M, Wabl M, Kanayama N, et al. Contribution of light chain rearrangement in peripheral B cells to the generation of high-affinity antibodies. Eur J Immunol. 2002;32:957-66 pubmed..Thus, our findings suggest that L chain rearrangement that occurs in the periphery can contribute to affinity maturation of Ab. ..
- Dougan S, Ashour J, Karssemeijer R, Popp M, Avalos A, Barisa M, et al. Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus. Nature. 2013;503:406-9 pubmed publisher..We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response. ..
- Selsing E, Storb U. Somatic mutation of immunoglobulin light-chain variable-region genes. Cell. 1981;25:47-58 pubmedA single germline immunoglobulin kappa-variable-region gene, VK167, is rearranged and expressed in two myelomas, MOPC167 and MOPC511. Only this single germline gene displays close homology to the expressed genes...
- Rankin A, Reed A, Oh S, Cozzo Picca C, Guay H, Larkin J, et al. CD4+ T cells recognizing a single self-peptide expressed by APCs induce spontaneous autoimmune arthritis. J Immunol. 2008;180:833-41 pubmed
- Seo S, Fields M, Buckler J, Reed A, Mandik Nayak L, Nish S, et al. The impact of T helper and T regulatory cells on the regulation of anti-double-stranded DNA B cells. Immunity. 2002;16:535-46 pubmed
- Elkabetz Y, Kerem A, Tencer L, Winitz D, Kopito R, Bar Nun S. Immunoglobulin light chains dictate vesicular transport-dependent and -independent routes for IgM degradation by the ubiquitin-proteasome pathway. J Biol Chem. 2003;278:18922-9 pubmed..dictates the degradative route taken by mu, we express in 70Z/3 pre-B cells either lambda ectopically or kappa by lipopolysaccharides-stimulated differentiation into B cells and show their assembly with mu heavy chains...
- Volgina V, Sun T, Bozek G, Martin T, Storb U. Scarcity of lambda 1 B cells in mice with a single point mutation in C lambda 1 is due to a low BCR signal caused by misfolded lambda 1 light chain. Mol Immunol. 2007;44:1417-28 pubmed..The reduction of lambda2,3 B cells in valine mice with a gamma2b transgene shows that the majority of their compensatory increase is almost entirely of the B1 cell type. ..
- Zhou X, Xiang Y, Ding X, Garrard W. A new hypersensitive site, HS10, and the enhancers, E3' and Ed, differentially regulate Ig? gene expression. J Immunol. 2012;188:2722-32 pubmed publisher..We conclude that the HS10, E3', and Ed differentially regulate Ig? gene dynamics. ..
- Hamlyn P, Browniee G, Cheng C, Gait M, Milstein C. Complete sequence of constant and 3' noncoding regions of an immunoglobulin mRNA using the dideoxynucleotide method of RNA sequencing. Cell. 1978;15:1067-75 pubmed..A revision of the amino acid sequence confirms the nucleic acid sequence. ..
- Schanke J, Van Ness B. Organization of the transcription factor binding sites in the kappa Ig intron enhancer. Effects of position, orientation, and spacing. J Immunol. 1994;153:4565-72 pubmedThe kappa Ig intron enhancer is comprised of multiple sequence motifs known to bind trans-acting factors that activate gene expression...
- Chang Y, Bosma G, Bosma M. Development of B cells in scid mice with immunoglobulin transgenes: implications for the control of V(D)J recombination. Immunity. 1995;2:607-16 pubmed..that certain immunoglobulin transgenes, specifically those which strongly inhibit endogenous VH-to-DJH and V kappa-to-J kappa rearrangement in wild-type mice, allow scid pro-B cells to progress to the pre-B and B cell stages...
- Fitzsimmons S, Bernstein R, Max E, Skok J, Shapiro M. Dynamic changes in accessibility, nuclear positioning, recombination, and transcription at the Ig kappa locus. J Immunol. 2007;179:5264-73 pubmed..Vkappa genes was increased in the silencer regions upstream of Jkappa1, within the Igkappa sterile transcript, the kappa constant region, the Ekappai and Ekappa3' enhancers, and the recombining sequence...
- Larijani M, Chen S, Cunningham L, Volpe J, Cowell L, Lewis S, et al. The recombination difference between mouse kappa and lambda segments is mediated by a pair-wise regulation mechanism. Mol Immunol. 2006;43:870-81 pubmedIn mice, kappa light chains dominate over lambda in the immunoglobulin repertoire by as much as 20-fold...
- Hewitt S, Farmer D, Marszalek K, Cadera E, Liang H, Xu Y, et al. Association between the Igk and Igh immunoglobulin loci mediated by the 3' Igk enhancer induces 'decontraction' of the Igh locus in pre-B cells. Nat Immunol. 2008;9:396-404 pubmed publisher..Our data indicate involvement of the Igk locus and its 3' enhancer in directing the Igh locus to a repressive nuclear subcompartment and inducing the Igh locus to decontract. ..
- Borrego A, Peters L, Jensen J, Ribeiro O, Koury Cabrera W, Starobinas N, et al. Genetic determinants of acute inflammation regulate Salmonella infection and modulate Slc11a1 gene (formerly Nramp1) effects in selected mouse lines. Microbes Infect. 2006;8:2766-71 pubmed..Typhimurium susceptibility QTL described in other mouse lines showed specific allele fixation in AIRmax or AIRmin mice, suggesting that these chromosomal regions also segregate with inflammatory phenotypes. ..
- Berland R, Fernandez L, Kari E, Han J, Lomakin I, Akira S, et al. Toll-like receptor 7-dependent loss of B cell tolerance in pathogenic autoantibody knockin mice. Immunity. 2006;25:429-40 pubmed..These results demonstrate that the particular threat of nucleic acid-containing autoantigens lies in their ability to bind both antigen receptor and TLR7. ..
- O Connor B, Vogel L, Zhang W, Loo W, Shnider D, Lind E, et al. Imprinting the fate of antigen-reactive B cells through the affinity of the B cell receptor. J Immunol. 2006;177:7723-32 pubmed..Thus, a continuum of elementary to comprehensive humoral immune responses exists that is controlled by inherent BCR affinity. ..
- D Hoostelaere L, Jouvin Marche E, Huppi K. Localization of CT beta and C kappa on mouse chromosome 6. Immunogenetics. 1985;22:277-83 pubmed..Originally the immunoglobulin kappa light chain (Igk) and the thymocyte surface antigens Lyt-2 and Lyt-3 were assigned to chromosome 6, and recently ..
- Miyazaki T, Kato I, Takeshita S, Karasuyama H, Kudo A. Lambda5 is required for rearrangement of the Ig kappa light chain gene in pro-B cell lines. Int Immunol. 1999;11:1195-202 pubmed..gene transfer into established lambda5-deficient pro-B cell lines induced rearrangement of the Ig kappa L chain genes after removal of IL-7 from the culture...
- Strohal R, Helmberg A, Kroemer G, Kofler R. Mouse Vk gene classification by nucleic acid sequence similarity. Immunogenetics. 1989;30:475-93 pubmed..Our data have implications for Vk gene analyses by nucleic acid hybridization and describe potentially important differences in sequence organization between VH and Vk genes. ..
- Liu Z, Widlak P, Zou Y, Xiao F, Oh M, Li S, et al. A recombination silencer that specifies heterochromatin positioning and ikaros association in the immunoglobulin kappa locus. Immunity. 2006;24:405-15 pubmed..Significantly, these are hallmarks of silenced endogenous germline Igkappa genes in B cells. These results lead us to propose that Sis participates in the monoallelic silencing aspect of allelic exclusion regulation. ..
- Faure M, Sanchez P, Cazenave P, Rueff Juy D. T cell tolerance to kappa light chain (L kappa): identification of a naturally processed self-C kappa-peptidic region by specific CD4+ T cell hybridomas obtained in L kappa-deficient mice. Cell Immunol. 1997;180:84-92 pubmedIn contrast to H-2d kappa light chain-deficient mice (kappa-/-), BALB/c (kappa+/+) mice fail to respond to kappa light chains (L kappa). This suggests that C kappa-specific T cells are tolerant to this self-antigen in kappa+/+ mice...
- Perng O, Aitken M, Rankin A, Garcia V, Kropf E, Erikson J, et al. The degree of CD4+ T cell autoreactivity determines cellular pathways underlying inflammatory arthritis. J Immunol. 2014;192:3043-56 pubmed publisher..These studies show that the degree of CD4(+) T cell reactivity for a self-peptide can play a prominent role in determining whether distinct cellular pathways can be targeted to prevent the development of inflammatory arthritis. ..
- Shalapour S, Lin X, Bastian I, Brain J, Burt A, Aksenov A, et al. Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity. Nature. 2017;551:340-345 pubmed publisher..These findings establish the importance of inflammation-induced suppression of cytotoxic CD8+ T-lymphocyte activation as a tumour-promoting mechanism. ..
- Steinel N, Lee B, Tubbs A, Bednarski J, Schulte E, Yang Iott K, et al. The ataxia telangiectasia mutated kinase controls Ig? allelic exclusion by inhibiting secondary V?-to-J? rearrangements. J Exp Med. 2013;210:233-9 pubmed publisher..Our data indicate that ATM kinases activated by RAG DSBs during Ig? recombination transduce transient H2AX/MDC1-independent signals that suppress initiation of further Ig? rearrangements to control Ig? allelic exclusion. ..
- Yamagami T, ten Boekel E, Schaniel C, Andersson J, Rolink A, Melchers F. Four of five RAG-expressing JCkappa-/- small pre-BII cells have no L chain gene rearrangements: detection by high-efficiency single cell PCR. Immunity. 1999;11:309-16 pubmed..They also show that a large part of the small pre-BII cells that express the rearrangement machinery can develop without IgL chain gene rearrangements. ..
- Chemin G, Tinguely A, Sirac C, Lechouane F, Duchez S, Cogne M, et al. Multiple RNA surveillance mechanisms cooperate to reduce the amount of nonfunctional Ig kappa transcripts. J Immunol. 2010;184:5009-17 pubmed publisher..Altogether, these data show that nonfunctionally rearranged alleles are subjected to active transcription but that multiple RNA surveillance mechanisms eradicate up to 90% of out-of-frame Igkappa mRNA. ..
- Zhou X, Xiang Y, Garrard W. The Ig? gene enhancers, E3' and Ed, are essential for triggering transcription. J Immunol. 2010;185:7544-52 pubmed publisher..Furthermore, these results reveal unexpected compensatory roles for Ed in E3' knockout mice in triggering germline transcription and V? gene rearrangements to both J? and RS elements. ..
- Malkiel S, Liao L, Cunningham M, Diamond B. T-Cell-dependent antibody response to the dominant epitope of streptococcal polysaccharide, N-acetyl-glucosamine, is cross-reactive with cardiac myosin. Infect Immun. 2000;68:5803-8 pubmed..We speculate that the pathogenic antibody response in rheumatic carditis may reflect the conversion of a T-cell-independent response to GlcNAc to a T-cell-dependent cross-reactive response to GlcNAc and myosin. ..
- Franco S, Murphy M, Li G, Borjeson T, Boboila C, Alt F. DNA-PKcs and Artemis function in the end-joining phase of immunoglobulin heavy chain class switch recombination. J Exp Med. 2008;205:557-64 pubmed publisher..We also find that under specific activation conditions, DNA-PKcs(-/-) B cells with chromosomal breaks are eliminated or at least prevented from progressing to metaphase via a p53-dependent response. ..
- Murphy A, Macdonald L, Stevens S, Karow M, Dore A, Pobursky K, et al. Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice. Proc Natl Acad Sci U S A. 2014;111:5153-8 pubmed publisher..use human variable region segments in their humoral responses by precisely replacing 6 Mb of mouse Ig heavy and kappa light variable region germ-line gene segments with their human counterparts while leaving the mouse constant ..
- Pricop L, Brumeanu T, Elahi E, Moran T, Wang B, Troustine M, et al. Antibody response elicited by T-dependent and T-independent antigens in gene targeted kappa-deficient mice. Int Immunol. 1994;6:1839-47 pubmed..the characteristics of antibody responses elicited by T-dependent and T-independent antigens in mice rendered kappa-deficient by targeted deletion of the J kappa C kappa gene segments...
- Xiang Y, Park S, Garrard W. V? gene repertoire and locus contraction are specified by critical DNase I hypersensitive sites within the V?-J? intervening region. J Immunol. 2013;190:1819-26 pubmed publisher..Thus, our studies demonstrate that DNase I hypersensitive sites HS1-2 within the V?-J? intervening region are essential for controlling locus contraction and creating a diverse Ab repertoire. ..
- Nicholson I, Zou X, Popov A, Cook G, Corps E, Humphries S, et al. Antibody repertoires of four- and five-feature translocus mice carrying human immunoglobulin heavy chain and kappa and lambda light chain yeast artificial chromosomes. J Immunol. 1999;163:6898-906 pubmedWe have produced mice that carry the human Ig heavy (IgH) and both kappa and lambda light chain transloci in a background in which the endogenous IgH and kappa loci have been inactivated...
- Havouis S, Dumas G, Ave P, Pritsch O, Huerre M, Dighiero G, et al. Negative regulation of autoreactive B cells in transgenic mice expressing a human pathogenic cold agglutinin. Eur J Immunol. 2000;30:2290-9 pubmed..The autoreactive B cells are amenable to polyclonal stimulation, making these transgenic mice a suitable model for a human autoimmune disease. ..
- Zhou X, Xiang Y, Ding X, Garrard W. Loss of an Ig? gene enhancer in mature B cells results in rapid gene silencing and partial reversible dedifferentiation. Mol Cell Biol. 2013;33:2091-101 pubmed publisher..This result establishes that receptor editing can occur in mature B cells and raises the possibility that this may provide a tolerance mechanism for eliminating autoreactive B cells in the periphery. ..
- Fields M, Hondowicz B, Metzgar M, Nish S, Wharton G, Picca C, et al. CD4+ CD25+ regulatory T cells inhibit the maturation but not the initiation of an autoantibody response. J Immunol. 2005;175:4255-64 pubmed..These studies indicate that CD25+ Treg cells act to inhibit the maturation, rather than the initiation, of autoantibody responses. ..
- Hauser A, Junt T, Mempel T, Sneddon M, Kleinstein S, Henrickson S, et al. Definition of germinal-center B cell migration in vivo reveals predominant intrazonal circulation patterns. Immunity. 2007;26:655-67 pubmed..The results suggest a revision to our views of B cell circulation within GCs and the functional relationship of its two major compartments. ..
- Pricop L, Hatakeyama A, Isobe H, Bona C. Analysis of lambda repertoire in kappa-deficient mice. Clin Immunol Immunopathol. 1995;76:S179-87 pubmed
- Schram B, Tze L, Ramsey L, Liu J, Najera L, Vegoe A, et al. B cell receptor basal signaling regulates antigen-induced Ig light chain rearrangements. J Immunol. 2008;180:4728-41 pubmed..These findings support a model whereby Ag-induced receptor editing is inhibited by BCR basal signaling on developing B cells; BCR down-regulation removes this basal signal, thereby initiating receptor editing. ..
- Bengtsson O, Daggfeldt A, Gronvik K, Andersson J. Maternal kappa-containing IgG induces a late anti-Kappa response in adult, Kappa-deficient offspring. Eur J Immunol. 2001;31:2652-9 pubmedb>Kappa (kappa)-light (L) chain-deficient (Ckappa-/-) mice readily mount a T cell-dependent antibody response after immunization with kappa-containing proteins...
- Xiang Y, Zhou X, Hewitt S, Skok J, Garrard W. A multifunctional element in the mouse Ig? locus that specifies repertoire and Ig loci subnuclear location. J Immunol. 2011;186:5356-66 pubmed publisher..Hence, Sis is a novel multifunctional element that specifies repertoire and heterochromatin localization to Ig genes. ..
- Benatuil L, Kaye J, Cretin N, Godwin J, Cariappa A, Pillai S, et al. Ig knock-in mice producing anti-carbohydrate antibodies: breakthrough of B cells producing low affinity anti-self antibodies. J Immunol. 2008;180:3839-48 pubmed..We suggest that in these mice, receptor editing functioned to lower the affinity for self-Ag below a threshold that would result in overt pathology, while allowing development of low affinity anti-self Abs. ..
- Tatu C, Ye J, Arnold L, Clarke S. Selection at multiple checkpoints focuses V(H)12 B cell differentiation toward a single B-1 cell specificity. J Exp Med. 1999;190:903-14 pubmed..This focus toward specificity for PtC facilitates the development of a large anti-PtC B-1 repertoire. ..