Igh

Summary

Gene Symbol: Igh
Description: immunoglobulin heavy chain complex
Species: mouse

Top Publications

  1. Guo C, Yoon H, Franklin A, Jain S, Ebert A, Cheng H, et al. CTCF-binding elements mediate control of V(D)J recombination. Nature. 2011;477:424-30 pubmed publisher
    Immunoglobulin heavy chain (IgH) variable region exons are assembled from V(H), D and J(H) gene segments in developing B lymphocytes. Within the 2...
  2. Coffey F, Alabyev B, Manser T. Initial clonal expansion of germinal center B cells takes place at the perimeter of follicles. Immunity. 2009;30:599-609 pubmed publisher
    ..The expanded clones were subsequently observed in the center of follicles, suggesting that GCs are created by coalescence of B cells from this follicular perimeter response. ..
  3. 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
    ..C-NHEJ indeed catalyses CSR joins, because C-NHEJ-deficient B cells had decreased CSR and substantial levels of IgH locus (immunoglobulin heavy chain, encoded by Igh) chromosomal breaks...
  4. Liu H, Schmidt Supprian M, Shi Y, Hobeika E, Barteneva N, Jumaa H, et al. Yin Yang 1 is a critical regulator of B-cell development. Genes Dev. 2007;21:1179-89 pubmed
    ..ablation of YY1 in mouse B cells caused a defect in somatic rearrangement in the immunoglobulin heavy-chain (IgH) locus and a block in the progenitor-B-to-precursor-B-cell transition, which was partially rescued by a ..
  5. Liu X, Wysocki L, Manser T. Autoantigen-B cell antigen receptor interactions that regulate expression of B cell antigen receptor Loci. J Immunol. 2007;178:5035-47 pubmed
    ..We propose that this adaptive process allows this class of autoreactive B cell to avoid conventional tolerance pathways and promotes development to mature phenotype. ..
  6. Bates J, Cado D, Nolla H, Schlissel M. Chromosomal position of a VH gene segment determines its activation and inactivation as a substrate for V(D)J recombination. J Exp Med. 2007;204:3247-56 pubmed
    ..These data suggest that locus contraction, mimicked by proximal targeting, can override any regulation imposed by DNA sequences immediately surrounding V(H) gene segments. ..
  7. 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
  8. Shih T, Roederer M, Nussenzweig M. Role of antigen receptor affinity in T cell-independent antibody responses in vivo. Nat Immunol. 2002;3:399-406 pubmed
  9. 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. ..
  10. Bothmer A, Robbiani D, Feldhahn N, Gazumyan A, Nussenzweig A, Nussenzweig M. 53BP1 regulates DNA resection and the choice between classical and alternative end joining during class switch recombination. J Exp Med. 2010;207:855-65 pubmed publisher
    ..We explore the role of 53BP1 in intrachromosomal DNA repair using I-SceI to introduce paired DSBs in the IgH locus...

Detail Information

Publications76

  1. Guo C, Yoon H, Franklin A, Jain S, Ebert A, Cheng H, et al. CTCF-binding elements mediate control of V(D)J recombination. Nature. 2011;477:424-30 pubmed publisher
    Immunoglobulin heavy chain (IgH) variable region exons are assembled from V(H), D and J(H) gene segments in developing B lymphocytes. Within the 2...
  2. Coffey F, Alabyev B, Manser T. Initial clonal expansion of germinal center B cells takes place at the perimeter of follicles. Immunity. 2009;30:599-609 pubmed publisher
    ..The expanded clones were subsequently observed in the center of follicles, suggesting that GCs are created by coalescence of B cells from this follicular perimeter response. ..
  3. 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
    ..C-NHEJ indeed catalyses CSR joins, because C-NHEJ-deficient B cells had decreased CSR and substantial levels of IgH locus (immunoglobulin heavy chain, encoded by Igh) chromosomal breaks...
  4. Liu H, Schmidt Supprian M, Shi Y, Hobeika E, Barteneva N, Jumaa H, et al. Yin Yang 1 is a critical regulator of B-cell development. Genes Dev. 2007;21:1179-89 pubmed
    ..ablation of YY1 in mouse B cells caused a defect in somatic rearrangement in the immunoglobulin heavy-chain (IgH) locus and a block in the progenitor-B-to-precursor-B-cell transition, which was partially rescued by a ..
  5. Liu X, Wysocki L, Manser T. Autoantigen-B cell antigen receptor interactions that regulate expression of B cell antigen receptor Loci. J Immunol. 2007;178:5035-47 pubmed
    ..We propose that this adaptive process allows this class of autoreactive B cell to avoid conventional tolerance pathways and promotes development to mature phenotype. ..
  6. Bates J, Cado D, Nolla H, Schlissel M. Chromosomal position of a VH gene segment determines its activation and inactivation as a substrate for V(D)J recombination. J Exp Med. 2007;204:3247-56 pubmed
    ..These data suggest that locus contraction, mimicked by proximal targeting, can override any regulation imposed by DNA sequences immediately surrounding V(H) gene segments. ..
  7. 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
  8. Shih T, Roederer M, Nussenzweig M. Role of antigen receptor affinity in T cell-independent antibody responses in vivo. Nat Immunol. 2002;3:399-406 pubmed
  9. 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. ..
  10. Bothmer A, Robbiani D, Feldhahn N, Gazumyan A, Nussenzweig A, Nussenzweig M. 53BP1 regulates DNA resection and the choice between classical and alternative end joining during class switch recombination. J Exp Med. 2010;207:855-65 pubmed publisher
    ..We explore the role of 53BP1 in intrachromosomal DNA repair using I-SceI to introduce paired DSBs in the IgH locus...
  11. Heltemes Harris L, Liu X, Manser T. Progressive surface B cell antigen receptor down-regulation accompanies efficient development of antinuclear antigen B cells to mature, follicular phenotype. J Immunol. 2004;172:823-33 pubmed
  12. 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
    Variable-(diversity)-joining (V(D)J) recombination at loci encoding the immunoglobulin heavy chain (Igh) and immunoglobulin light chain (Igk) takes place sequentially during successive stages in B cell development...
  13. Kitano M, Moriyama S, Ando Y, Hikida M, Mori Y, Kurosaki T, et al. Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity. Immunity. 2011;34:961-72 pubmed publisher
    ..These results clarify the role of Bcl6 in pre-GC B cell dynamics and highlight the modulation of Bcl6 expression in Tfh cells that persist in the late phase of the antibody response. ..
  14. Allen C, Okada T, Tang H, Cyster J. Imaging of germinal center selection events during affinity maturation. Science. 2007;315:528-31 pubmed
    ..On the basis of these observations, we propose a model in which competition for T cell help plays a more dominant role in the selection of GC B cells than previously appreciated...
  15. Tinguely A, Chemin G, Peron S, Sirac C, Reynaud S, Cogne M, et al. Cross talk between immunoglobulin heavy-chain transcription and RNA surveillance during B cell development. Mol Cell Biol. 2012;32:107-17 pubmed publisher
    ..Here, we tracked transcription and posttranscriptional regulation for both Ig heavy-chain (IgH) alleles in mice carrying a nonfunctional knock-in allele...
  16. Xu S, Wong S, Lam K. Cutting edge: B cell linker protein is dispensable for the allelic exclusion of immunoglobulin heavy chain locus but required for the persistence of CD5+ B cells. J Immunol. 2000;165:4153-7 pubmed
    ..This suggests that BLNK deficiency affects not only the generation but also the persistence of B-1 cells. ..
  17. Taki S, Meiering M, Rajewsky K. Targeted insertion of a variable region gene into the immunoglobulin heavy chain locus. Science. 1993;262:1268-71 pubmed
    ..Immunoglobulin transgenic mice generated in this fashion by gene targeting should prove useful for the exploration of immunoregulatory mechanisms. ..
  18. Vincent Fabert C, Fiancette R, Pinaud E, Truffinet V, Cogne N, Cogne M, et al. Genomic deletion of the whole IgH 3' regulatory region (hs3a, hs1,2, hs3b, and hs4) dramatically affects class switch recombination and Ig secretion to all isotypes. Blood. 2010;116:1895-8 pubmed publisher
    The immunoglobulin heavy chain locus (IgH) undergoes multiple changes along B-cell differentiation. In progenitor B cells, V(D)J assembly allows expression of ? heavy chains...
  19. Pinaud E, Khamlichi A, Le Morvan C, Drouet M, Nalesso V, Le Bert M, et al. Localization of the 3' IgH locus elements that effect long-distance regulation of class switch recombination. Immunity. 2001;15:187-99 pubmed
    ..in the 3' region have shown that both hs3a and hs1,2 are dispensable for normal expression and rearrangement of the IgH locus but that their replacement with a transcribed neo gene severely affects class switch recombination...
  20. Fukita Y, Jacobs H, Rajewsky K. Somatic hypermutation in the heavy chain locus correlates with transcription. Immunity. 1998;9:105-14 pubmed
    Three mutant immunoglobulin heavy chain (IgH) insertion mice were generated in which a targeted nonfunctional IgH passenger transgene was either devoid of promoter (pdelta) or was placed under the transcriptional control of either its ..
  21. Ji Y, Resch W, Corbett E, Yamane A, Casellas R, Schatz D. The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell. 2010;141:419-31 pubmed publisher
    ..a highly focal manner to a small region of active chromatin encompassing Ig kappa and Tcr alpha J gene segments and Igh and Tcr beta J and J-proximal D gene segments...
  22. Waisman A, Kraus M, Seagal J, Ghosh S, Melamed D, Song J, et al. IgG1 B cell receptor signaling is inhibited by CD22 and promotes the development of B cells whose survival is less dependent on Ig alpha/beta. J Exp Med. 2007;204:747-58 pubmed
    ..gamma1-driven B cell development is disfavored in competition with developing B cells expressing a wild-type (WT) IgH locus...
  23. Fuxa M, Skok J, Souabni A, Salvagiotto G, Roldan E, Busslinger M. Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene. Genes Dev. 2004;18:411-22 pubmed
    The subnuclear location and chromatin state of the immunoglobulin heavy-chain (IgH) locus have been implicated in the control of VDJ recombination...
  24. Reina San Martin B, Difilippantonio S, Hanitsch L, Masilamani R, Nussenzweig A, Nussenzweig M. H2AX is required for recombination between immunoglobulin switch regions but not for intra-switch region recombination or somatic hypermutation. J Exp Med. 2003;197:1767-78 pubmed
    ..Our results suggest a role for H2AX in regulating the higher order chromatin remodeling that facilitates switch region synapsis. ..
  25. Casola S, Otipoby K, Alimzhanov M, Humme S, Uyttersprot N, Kutok J, et al. B cell receptor signal strength determines B cell fate. Nat Immunol. 2004;5:317-27 pubmed
    ..Mice carrying a targeted replacement of Igh by LMP2A leading to high or low expression of the LMP2A protein developed B-1 or follicular and marginal zone B ..
  26. Reynaud S, Delpy L, Fleury L, Dougier H, Sirac C, Cogne M. Interallelic class switch recombination contributes significantly to class switching in mouse B cells. J Immunol. 2005;174:6176-83 pubmed
  27. 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. ..
  28. Schelonka R, Ivanov I, Jung D, Ippolito G, Nitschke L, Zhuang Y, et al. A single DH gene segment creates its own unique CDR-H3 repertoire and is sufficient for B cell development and immune function. J Immunol. 2005;175:6624-32 pubmed
    ..1 in the DH locus. We term this D-limited IgH allele DeltaD-DFL...
  29. Bolland D, Wood A, Afshar R, Featherstone K, Oltz E, Corcoran A. Antisense intergenic transcription precedes Igh D-to-J recombination and is controlled by the intronic enhancer Emu. Mol Cell Biol. 2007;27:5523-33 pubmed
    ..We previously proposed that antisense intergenic transcription, activated throughout the mouse Igh VH region in pro-B cells, remodels chromatin for VH-to-DJH recombination...
  30. Delpy L, Le Bert M, Cogne M, Khamlichi A. Germ-line transcription occurs on both the functional and the non-functional alleles of immunoglobulin constant heavy chain genes. Eur J Immunol. 2003;33:2108-13 pubmed
    ..Here, we provide evidence that germ-line transcription occurs on both the functional and the non-functional alleles. ..
  31. 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
    ..DP-T/HC/LC mice were severely deficient for all serum IgH isotypes except IgM and, unexpectedly, IgG1...
  32. Gu Y, Seidl K, Rathbun G, Zhu C, Manis J, van der Stoep N, et al. Growth retardation and leaky SCID phenotype of Ku70-deficient mice. Immunity. 1997;7:653-65 pubmed
    ..These unanticipated features of the Ku70-deficient phenotype with respect to lymphocyte development and V(D)J recombination may reflect differential functions of the three DNA-PK components. ..
  33. Jhunjhunwala S, van Zelm M, Peak M, Cutchin S, Riblet R, van Dongen J, et al. The 3D structure of the immunoglobulin heavy-chain locus: implications for long-range genomic interactions. Cell. 2008;133:265-79 pubmed publisher
    The immunoglobulin heavy-chain (Igh) locus is organized into distinct regions that contain multiple variable (V(H)), diversity (D(H)), joining (J(H)) and constant (C(H)) coding elements...
  34. Degner S, Verma Gaur J, Wong T, Bossen C, Iverson G, Torkamani A, et al. CCCTC-binding factor (CTCF) and cohesin influence the genomic architecture of the Igh locus and antisense transcription in pro-B cells. Proc Natl Acad Sci U S A. 2011;108:9566-71 pubmed publisher
    Compaction and looping of the ~2.5-Mb Igh locus during V(D)J rearrangement is essential to allow all V(H) genes to be brought in proximity with D(H)-J(H) segments to create a diverse antibody repertoire, but the proteins directly ..
  35. Yang Q, Riblet R, Schildkraut C. Sites that direct nuclear compartmentalization are near the 5' end of the mouse immunoglobulin heavy-chain locus. Mol Cell Biol. 2005;25:6021-30 pubmed
    VDJ rearrangement in the mouse immunoglobulin heavy chain (Igh) locus involves a combination of events, including a large change in its nuclear compartmentalization...
  36. Morvan C, Pinaud E, Decourt C, Cuvillier A, Cogne M. The immunoglobulin heavy-chain locus hs3b and hs4 3' enhancers are dispensable for VDJ assembly and somatic hypermutation. Blood. 2003;102:1421-7 pubmed
  37. Zarrin A, Del Vecchio C, Tseng E, Gleason M, Zarin P, Tian M, et al. Antibody class switching mediated by yeast endonuclease-generated DNA breaks. Science. 2007;315:377-81 pubmed
    ..cytidine deaminase (AID)-dependent double-strand breaks (DSBs) within two large immunoglobulin heavy chain (IgH) locus switch (S) regions that lie up to 200 kilobases apart...
  38. Pewzner Jung Y, Friedmann D, Sonoda E, Jung S, Rajewsky K, Eilat D. B cell deletion, anergy, and receptor editing in "knock in" mice targeted with a germline-encoded or somatically mutated anti-DNA heavy chain. J Immunol. 1998;161:4634-45 pubmed
    ..Clonal anergy may serve as a back-up mechanism for central tolerance, or it may represent an intermediate step in clonal deletion. ..
  39. Peron S, Laffleur B, Denis Lagache N, Cook Moreau J, Tinguely A, Delpy L, et al. AID-driven deletion causes immunoglobulin heavy chain locus suicide recombination in B cells. Science. 2012;336:931-4 pubmed publisher
    ..The frequency of this event is approaching that of class switching and makes it a potential regulator of B cell homeostasis. ..
  40. Young F, Ardman B, Shinkai Y, Lansford R, Blackwell T, Mendelsohn M, et al. Influence of immunoglobulin heavy- and light-chain expression on B-cell differentiation. Genes Dev. 1994;8:1043-57 pubmed
  41. Bebin A, Carrion C, Marquet M, Cogne N, Lecardeur S, Cogne M, et al. In vivo redundant function of the 3' IgH regulatory element HS3b in the mouse. J Immunol. 2010;184:3710-7 pubmed publisher
    In the mouse, the regulatory region located at the 3' end of the IgH locus includes four transcriptional enhancers: HS3a, HS1-2, HS3b, and HS4; the first three lie in a quasi-palindromic structure...
  42. 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
    ..Thus, Ku80 is essential for switch recombination in vivo, suggesting a significant overlap between the molecular machinery that mediates DNA DSB repair, V(D)J recombination and isotype switching. ..
  43. Haynes N, Allen C, Lesley R, Ansel K, Killeen N, Cyster J. Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation. J Immunol. 2007;179:5099-108 pubmed
  44. 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. ..
  45. Rouaud P, Vincent Fabert C, Saintamand A, Fiancette R, Marquet M, Robert I, et al. The IgH 3' regulatory region controls somatic hypermutation in germinal center B cells. J Exp Med. 2013;210:1501-7 pubmed publisher
    ..The contribution of IgH transcriptional enhancers in SHM is unclear...
  46. Fiancette R, Rouaud P, Vincent Fabert C, Laffleur B, Magnone V, Cogne M, et al. A p53 defect sensitizes various stages of B cell development to lymphomagenesis in mice carrying an IgH 3' regulatory region-driven c-myc transgene. J Immunol. 2011;187:5772-82 pubmed publisher
    ..After translocation into the IgH locus, c-myc is constitutively expressed under the control of active IgH enhancers...
  47. Good Jacobson K, Szumilas C, Chen L, Sharpe A, Tomayko M, Shlomchik M. PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol. 2010;11:535-42 pubmed publisher
    ..PD-1 expression on T cells and PD-L2 expression on B cells controlled T(FH) cell and PC numbers. Thus, PD-1 regulates selection and survival in the GC, affecting the quantity and quality of long-lived PCs. ..
  48. Ramiro A, Jankovic M, Callen E, Difilippantonio S, Chen H, McBride K, et al. Role of genomic instability and p53 in AID-induced c-myc-Igh translocations. Nature. 2006;440:105-9 pubmed
    ..Here we find that translocations between c-myc and the IgH locus (Igh) are induced in primary B cells within hours of expression of the catalytically active form of ..
  49. Manis J, Gu Y, Lansford R, Sonoda E, Ferrini R, Davidson L, et al. Ku70 is required for late B cell development and immunoglobulin heavy chain class switching. J Exp Med. 1998;187:2081-9 pubmed
    ..We conclude that Ku70 is required for the generation of B cells that have undergone Ig HC class switching. Potential roles for Ku70 in the CSR process are discussed. ..
  50. Schebesta A, McManus S, Salvagiotto G, Delogu A, Busslinger G, Busslinger M. Transcription factor Pax5 activates the chromatin of key genes involved in B cell signaling, adhesion, migration, and immune function. Immunity. 2007;27:49-63 pubmed
  51. Loffert D, Ehlich A, Muller W, Rajewsky K. Surrogate light chain expression is required to establish immunoglobulin heavy chain allelic exclusion during early B cell development. Immunity. 1996;4:133-44 pubmed
    Allelic exclusion at the IgH locus was examined in B lineage cells of wild-type mice and mice unable to express the surrogate light chain molecule lambda 5 using a single-cell PCR approach...
  52. Callen 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. ..
  53. Afshar R, Pierce S, Bolland D, Corcoran A, Oltz E. Regulation of IgH gene assembly: role of the intronic enhancer and 5'DQ52 region in targeting DHJH recombination. J Immunol. 2006;176:2439-47 pubmed
    ..Paradoxically, germline deletions of the IgH enhancer (Emu) only modestly reduce D(H)-->J(H) rearrangements when assessed in peripheral B cells...
  54. Robbiani D, Bothmer A, Callen E, Reina San Martin B, Dorsett Y, Difilippantonio S, et al. AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations. Cell. 2008;135:1028-38 pubmed publisher
    ..of the most well characterized oncogenic translocations juxtaposes c-myc and the immunoglobulin heavy-chain locus (IgH) and is found in Burkitt's lymphomas in humans and plasmacytomas in mice...
  55. Vincent Fabert C, Truffinet V, Fiancette R, Cogne N, Cogne M, Denizot Y. Ig synthesis and class switching do not require the presence of the hs4 enhancer in the 3' IgH regulatory region. J Immunol. 2009;182:6926-32 pubmed publisher
    Several studies have reported that regulatory elements located 3' of the IgH locus (namely hs3a, hs1,2, hs3b, and hs4) might play a role during class switch recombination (CSR) and Ig synthesis...
  56. Lutz J, Heideman M, Roth E, van den Berk P, Muller W, Raman C, et al. Pro-B cells sense productive immunoglobulin heavy chain rearrangement irrespective of polypeptide production. Proc Natl Acad Sci U S A. 2011;108:10644-9 pubmed publisher
    ..Ig rearrangement begins in pro-B cells at the IgH locus...
  57. Boboila C, Yan C, Wesemann D, Jankovic M, Wang J, Manis J, et al. Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4. J Exp Med. 2010;207:417-27 pubmed publisher
    ..During IgH class switch recombination (CSR) in B lymphocytes, switch (S) region DSBs are joined by C-NHEJ to form junctions ..
  58. 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
    ..In the absence of either factor, B cells activated for CSR frequently generate AID-dependent IgH locus chromosomal breaks and translocations...
  59. Victora G, Schwickert T, Fooksman D, Kamphorst A, Meyer Hermann M, Dustin M, et al. Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell. 2010;143:592-605 pubmed publisher
    ..Thus, T cell help, and not direct competition for antigen, is the limiting factor in GC selection...
  60. Cogne M, Lansford R, Bottaro A, Zhang J, Gorman J, Young F, et al. A class switch control region at the 3' end of the immunoglobulin heavy chain locus. Cell. 1994;77:737-47 pubmed
    We replaced the IgH 3' enhancer (3'EH) region with a neomycin resistance gene in ES cells and generated chimeric mice in which all mature lymphocytes were either heterozygous (3'EH+/-) or homozygous (3'EH-/-) for the mutation...
  61. 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
    Mice carrying transgenic rearranged V region genes in their IgH and Igkappa loci to encode an autoreactive specificity direct the emerging autoreactive progenitors into a pre-B cell compartment, in which their receptors are edited by ..
  62. Chiarle R, Zhang Y, Frock R, Lewis S, Molinie B, Ho Y, et al. Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell. 2011;147:107-19 pubmed publisher
    ..involving fixed I-SceI meganuclease-generated DNA double-strand breaks (DSBs) within the c-myc oncogene or IgH locus of B lymphocytes induced for activation-induced cytidine deaminase (AID)-dependent IgH class switching...
  63. Wang J, Boxer L. Regulatory elements in the immunoglobulin heavy chain gene 3'-enhancers induce c-myc deregulation and lymphomagenesis in murine B cells. J Biol Chem. 2005;280:12766-73 pubmed
    ..translocations that juxtapose the c-myc proto-oncogene with regulatory elements of the immunoglobulin heavy (IgH) or light chain loci resulting in the deregulation of c-myc expression...
  64. Lansford R, Manis J, Sonoda E, Rajewsky K, Alt F. Ig heavy chain class switching in Rag-deficient mice. Int Immunol. 1998;10:325-32 pubmed
    ..Together, these findings indicate that neither RAG-1 nor RAG-2 expression is required for efficient class switching to most HC isotypes in B cells. ..
  65. Dunnick W, Collins J, Shi J, Westfield G, Fontaine C, Hakimpour P, et al. Switch recombination and somatic hypermutation are controlled by the heavy chain 3' enhancer region. J Exp Med. 2009;206:2613-23 pubmed publisher
    ..Finally, we find that in B cells with a transgene lacking the 3' enhancers, interchromosomal recombination between the transgenic VDJ exon and the endogenous heavy chain C genes is more easily detected than CSR within the transgene. ..
  66. Lam K, Kuhn R, Rajewsky K. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell. 1997;90:1073-83 pubmed
    ..Ablation leads to rapid death of mature B lymphocytes, which is preceded by down-regulation of MHC antigens and up-regulation of CD95 (Fas) and can be delayed by constitutive bcl-2 expression. ..
  67. Su I, Basavaraj A, Krutchinsky A, Hobert O, Ullrich A, Chait B, et al. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol. 2003;4:124-31 pubmed
    ..a critical role for Ezh2 in early B cell development and rearrangement of the immunoglobulin heavy chain gene (Igh). We also revealed Ezh2 as a key regulator of histone H3 methylation in early B cell progenitors...
  68. 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. ..
  69. Srinivasan L, Sasaki Y, Calado D, Zhang B, Paik J, Depinho R, et al. PI3 kinase signals BCR-dependent mature B cell survival. Cell. 2009;139:573-86 pubmed publisher
  70. 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. ..
  71. 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. ..
  72. Nitschke L, Kestler J, Tallone T, Pelkonen S, Pelkonen J. Deletion of the DQ52 element within the Ig heavy chain locus leads to a selective reduction in VDJ recombination and altered D gene usage. J Immunol. 2001;166:2540-52 pubmed
    ..We propose a model in which the DQ52 promoter region enhances the induction of secondary DJ rearrangements. ..
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    ..That bacteria-derived LPS could circumvent these controls may explain the well-known association between autoantibody-mediated diseases and episodes of systemic infection. ..