Skip to main content

Advertisement

SpringerLink
Log in

Autoreactive B Cells and Epigenetics

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Autoreactive B cells are central in the pathogenesis of autoimmune diseases (AID) not only by producing autoantibodies but also by secreting cytokines and by presenting autoantigens. Changes in DNA methylation, histone modifications, and miRNA expression, the hallmarks of epigenetic failure, characterize B cells isolated from patients with AID, highlighting the contribution of epigenetic processes to autoreactivity. Additional evidence of epigenetic involvement in the development of B cell autoreactivity comes from in vivo and in vitro studies using DNA demethylating agents as accelerating factors or histone deacetylase inhibitors as repressing factors. As a result, a better understanding of the altered epigenetic processes in AID and in particular in B cells opens perspectives for the development of new therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

AID:

Autoimmune diseases

SLE:

Systemic lupus erythematosus

RA:

Rheumatoid arthritis

DNMT:

DNA methyltransferase

HDAC:

Histone deacetylase

miR:

MicroRNA

References

  1. Hom G, Graham RR, Modrek B et al (2008) Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med 358:900–909

    Article  PubMed  CAS  Google Scholar 

  2. Fraga MF, Ballestar E, Paz MF et al (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A 102:10604–10609

    Article  PubMed  CAS  Google Scholar 

  3. Garaud S, Le Dantec C, Jousse-Joulin S et al (2009) IL-6 modulates CD5 expression in B cells from patients with lupus by regulating DNA methylation. J Immunol 182:5623–5632

    Article  PubMed  CAS  Google Scholar 

  4. Balada E, Ordi-Ros J, Vilardell-Tarrés M (2007) DNA methylation and systemic lupus erythematosus. Ann N Y Acad Sci 1108:127–136

    Article  PubMed  CAS  Google Scholar 

  5. Richardson B, Scheinbart L, Strahler J, Gross L, Hanash S, Johnson M (1990) Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 33:1665–1673

    Article  PubMed  CAS  Google Scholar 

  6. Neidhart M, Rethage J, Kuchen S et al (2000) Retrotransposable L1 elements expressed in rheumatoid arthritis synovial tissue: association with genomic DNA hypomethylation and influence on gene expression. Arthritis Rheum 43:2634–2647

    Article  PubMed  CAS  Google Scholar 

  7. Lee YH, Rho YH, Choi SJ, Ji JD, Song GG (2007) PADI4 polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Rheumatol Int 27:827–833

    Article  PubMed  CAS  Google Scholar 

  8. Webb R, Wren JD, Jeffries M et al (2009) Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus. Arthritis Rheum 60:1076–1084

    Article  PubMed  CAS  Google Scholar 

  9. Sawalha AH, Webb R, Han S et al (2008) Common variants within MECP2 confer risk of systemic lupus erythematosus. PLoS ONE 3:e1727

    Article  PubMed  CAS  Google Scholar 

  10. Chen CZ, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86

    Article  PubMed  CAS  Google Scholar 

  11. Lindsay MA (2008) MicroRNAs and the immune response. Trends Immunol 29:343–351

    Article  PubMed  CAS  Google Scholar 

  12. Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK (2008) Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther 10:R101

    Article  PubMed  Google Scholar 

  13. Nakasa T, Miyaki S, Okubo A et al (2008) Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum 58:1284–1292

    Article  PubMed  CAS  Google Scholar 

  14. Tang Y, Luo X, Cui H et al (2009) MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum 60:1065–1075

    Article  PubMed  CAS  Google Scholar 

  15. Dai Y, Huang YS, Tang M et al (2007) Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus 16:939–946

    Article  PubMed  CAS  Google Scholar 

  16. Dai Y, Sui W, Lan H, Yan Q, Huang H, Huang Y (2008) Comprehensive analysis of microRNA expression patterns in renal biopsies of lupus nephritis patients. Rheumatol Int . doi:10.1007/s00296-008-0758-6

    Google Scholar 

  17. Danbara M, Kameyama K, Higashihara M, Takagaki Y (2002) DNA methylation dominates transcriptional silencing of Pax5 in terminally differentiated B cell lines. Mol Immunol 38:1161–1166

    Article  PubMed  CAS  Google Scholar 

  18. Amaravadi L, Klemsz MJ (1999) DNA methylation and chromatin structure regulate PU.1 expression. DNA Cell Biol 18:875–884

    Article  PubMed  CAS  Google Scholar 

  19. Maier H, Colbert J, Fitzsimmons D, Clark DR, Hagman J (2003) Activation of the early B-cell-specific mb-1 (Ig-alpha) gene by Pax-5 is dependent on an unmethylated Ets binding site. Mol Cell Biol 23:1946–1960

    Article  PubMed  CAS  Google Scholar 

  20. Walter K, Bonifer C, Tagoh H (2008) Stem cell-specific epigenetic priming and B cell-specific transcriptional activation at the mouse Cd19 locus. Blood 112:1673–1682

    Article  PubMed  CAS  Google Scholar 

  21. Schwab J, Illges H (2001) Silencing of CD21 expression in synovial lymphocytes is independent of methylation of the CD21 promoter CpG island. Rheumatol Int 20:133–137

    Article  PubMed  CAS  Google Scholar 

  22. O’Carroll D, Mecklenbrauker I, Das PP et al (2007) A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev 21:1999–2004

    Article  PubMed  CAS  Google Scholar 

  23. Koralov SB, Muljo SA, Galler GR et al (2008) Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell 132:860–874

    Article  PubMed  CAS  Google Scholar 

  24. Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD (2008) MicroRNAs: new regulators of immune cell development and function. Nat Immunol 9:839–845

    Article  PubMed  CAS  Google Scholar 

  25. Thai TH, Calado DP, Casola S et al (2007) Regulation of the germinal center response by microRNA-155. Science 316:604–608

    Article  PubMed  CAS  Google Scholar 

  26. Rodriguez A, Vigorito E, Clare S et al (2007) Requirement of bic/microRNA-155 for normal immune function. Science 316:608–611

    Article  PubMed  CAS  Google Scholar 

  27. Xiao C, Calado DP, Galler G et al (2007) MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell 131:146–159

    Article  PubMed  CAS  Google Scholar 

  28. Baxter J, Sauer S, Peters A et al (2004) Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes. EMBO J 23:4462–4472

    Article  PubMed  CAS  Google Scholar 

  29. Estève PO, Chin HG, Smallwood A et al (2006) Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication. Genes Dev 20:3089–3103

    Article  PubMed  CAS  Google Scholar 

  30. Thomas LR, Miyashita H, Cobb RM et al (2008) Functional analysis of histone methyltransferase g9a in B and T lymphocytes. J Immunol 181:485–493

    PubMed  CAS  Google Scholar 

  31. Ehrlich M, Jackson K, Weemaes C (2006) Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF). Orphanet J Rare Dis 1:2

    Article  PubMed  Google Scholar 

  32. Blanco-Betancourt CE, Moncla A, Milili M et al (2004) Defective B-cell-negative selection and terminal differentiation in the ICF syndrome. Blood 103:2683–2690

    Article  PubMed  CAS  Google Scholar 

  33. Jin B, Tao Q, Peng J et al (2008) DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function. Hum Mol Genet 17:690–709

    Article  PubMed  CAS  Google Scholar 

  34. Ehrlich M, Sanchez C, Shao C et al (2008) ICF, an immunodeficiency syndrome: DNA methyltransferase 3B involvement, chromosome anomalies, and gene dysregulation. Autoimmunity 41:253–271

    Article  PubMed  CAS  Google Scholar 

  35. Lee SC, Bottaro A, Insel RA (2003) Activation of terminal B cell differentiation by inhibition of histone deacetylation. Mol Immunol 39:923–932

    Article  PubMed  CAS  Google Scholar 

  36. Yu J, Angelin-Duclos C, Greenwood J, Liao J, Calame K (2000) Transcriptional repression by blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase. Mol Cell Biol 20:2592–2603

    Article  PubMed  CAS  Google Scholar 

  37. Ancelin K, Lange UC, Hajkova P et al (2006) Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nat Cell Biol 8:623–630

    Article  PubMed  CAS  Google Scholar 

  38. Gyory I, Wu J, Fejér G, Seto E, Wright KL (2004) PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing. Nat Immunol 5:299–308

    Article  PubMed  CAS  Google Scholar 

  39. Xu CR, Feeney AJ (2009) The epigenetic profile of Ig genes is dynamically regulated during B cell differentiation and is modulated by pre-B cell receptor signaling. J Immunol 182:1362–1369

    Article  PubMed  CAS  Google Scholar 

  40. Espinoza CR, Feeney AJ (2007) Chromatin accessibility and epigenetic modifications differ between frequently and infrequently rearranging VH genes. Mol Immunol 44:2675–2685

    Article  PubMed  CAS  Google Scholar 

  41. Nakase H, Takahama Y, Akamatsu Y (2003) Effect of CpG methylation on RAG1/RAG2 reactivity: implications of direct and indirect mechanisms for controlling V(D)J cleavage. EMBO 4:774–780

    Article  CAS  Google Scholar 

  42. Larijani M, Frieder D, Sonbuchner TM et al (2005) Methylation protects cytidines from AID-mediated deamination. Mol Immunol 42:599–604

    Article  PubMed  CAS  Google Scholar 

  43. Odegard VH, Kim ST, Anderson SM, Shlomchik MJ, Schatz DG (2005) Histone modifications associated with somatic hypermutation. Immunity 23:101–110

    Article  PubMed  CAS  Google Scholar 

  44. Youinou P, Taher TE, Pers JO, Mageed RA, Renaudineau Y (2009) B-lymphocyte cytokines and rheumatic autoimmune disease. Arthritis Rheum 60:1873–1880

    Article  PubMed  CAS  Google Scholar 

  45. Harris DP, Haynes L, Sayles PC et al (2000) Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol 1:475–482

    Article  PubMed  CAS  Google Scholar 

  46. Pang Y, Norihisa Y, Benjamin D, Kantor RR, Young HA (1992) Interferon-gamma gene expression in human B-cell lines: induction by interleukin-2, protein kinase C activators, and possible effect of hypomethylation on gene regulation. Blood 80:724–732

    PubMed  CAS  Google Scholar 

  47. Janson PC, Marits P, Thörn M, Ohlsson R, Winqvist O (2008) CpG methylation of the IFNG gene as a mechanism to induce immunosuppression [correction of immunosupression] in tumor-infiltrating lymphocytes. J Immunol 181:2878–2886

    PubMed  CAS  Google Scholar 

  48. Yamamoto I, Matsunaga T, Sakata K, Nakamura Y, Doi S, Hanmyou F (1996) Histone hyperacetylation plays a role in augmentation of IL-4-induced IgE production in LPS-stimulated murine B-lymphocytes by sodium butyrate. J Biochem 119:1056–1061

    PubMed  CAS  Google Scholar 

  49. Cannat A, Seligmann M (1968) Induction by isoniazid and hydrallazine of antinuclear factors in mice. Clin Exp Immunol 3:99–105

    PubMed  CAS  Google Scholar 

  50. Ten Veen JH, Feltkamp TE (1972) Studies on drug induced lupus erythematosus in mice. I. Drug induced antinuclear antibodies (ANA). Clin Exp Immunol 11:265–276

    PubMed  Google Scholar 

  51. Dubroff LM, Reid RJ Jr (1980) Hydralazine-pyrimidine interactions may explain hydralazine-induced lupus erythematosus. Sciences 208:404–406

    CAS  Google Scholar 

  52. Lee BH, Yegnasubramanian S, Lin X, Nelson WG (2005) Procainamide is a specific inhibitor of DNA methyltransferase 1. J Biol Chem 280:40749–40756

    Article  PubMed  CAS  Google Scholar 

  53. Deng C, Lu Q, Zhang Z et al (2003) Hydralazine may induce autoimmunity by inhibiting extracellular signal-regulated kinase pathway signaling. Arthritis Rheum 48:746–756

    Article  PubMed  CAS  Google Scholar 

  54. Quddus J, Johnson KJ, Gavalchin J et al (1993) Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice. J Clin Invest 92:38–53

    Article  PubMed  CAS  Google Scholar 

  55. Yung RL, Quddus J, Chrisp CE, Johnson KJ, Richardson BC (1995) Mechanism of drug-induced lupus. I. Cloned Th2 cells modified with DNA methylation inhibitors in vitro cause autoimmunity in vivo. J Immunol 154:3025–3035

    PubMed  CAS  Google Scholar 

  56. Mazari L, Ouarzane M, Zouali M (2007) Subversion of B lymphocyte tolerance by hydralazine, a potential mechanism for drug-induced lupus. Proc Natl Acad Sci U S A 104:6317–6322

    Article  PubMed  CAS  Google Scholar 

  57. Bauer VW, Squire TL, Lowe ME, Andrews MT (2001) Expression of a chimeric retroviral-lipase mRNA confers enhanced lipolysis in a hibernating mammal. Am J Physiol Regul Integr Comp Physiol 281:R1186–R1192

    PubMed  CAS  Google Scholar 

  58. Wu J, Zhou T, He J, Mountz JD (1993) Autoimmune disease in mice due to integration of an endogenous retrovirus in an apoptosis gene. J Exp Med 178:461–468

    Article  PubMed  CAS  Google Scholar 

  59. Qian Y, Santiago C, Borrero M, Tedder TF, Clarke SH (2001) Lupus-specific antiribonucleoprotein B cell tolerance in nonautoimmune mice is maintained by differentiation to B-1 and governed by B cell receptor signaling thresholds. J Immunol 166:2412–2419

    PubMed  CAS  Google Scholar 

  60. Hippen KL, Tze LE, Behrens TW (2000) CD5 maintains tolerance in anergic B cells. J Exp Med 191:883–890

    Article  PubMed  CAS  Google Scholar 

  61. Jamin C, Magadur G, Lamour A et al (1992) Cell-free CD5 in patients with rheumatic diseases. Immunol Lett 31:79–83

    Article  PubMed  CAS  Google Scholar 

  62. Lu X, Axtell RC, Collawn JF, Gibson A, Justement LB, Raman C (2002) AP2 adaptor complex-dependent internalization of CD5: differential regulation in T and B cells. J Immunol 168:5612–5620

    PubMed  CAS  Google Scholar 

  63. Renaudineau Y, Hillion S, Saraux A, Mageed RA, Youinou P (2005) An alternative exon 1 of the CD5 gene regulates CD5 expression in human B lymphocytes. Blood 106:2781–2789

    Article  PubMed  CAS  Google Scholar 

  64. Garaud S, Le Dantec C, Berthou C, Lydyard PM, Youinou P, Renaudineau Y (2008) Selection of the alternative exon 1 from the cd5 gene down-regulates membrane level of the protein in B lymphocytes. J Immunol 181:2010–2018

    PubMed  CAS  Google Scholar 

  65. Renaudineau Y, Vallet S, Le Dantec C, Hillion S, Saraux A, Youinou P (2005) Characterization of the human CD5 endogenous retrovirus-E in B lymphocytes. Genes Immun 6:663–671

    PubMed  CAS  Google Scholar 

  66. Pullmann R Jr, Bonilla E, Phillips PE, Middleton FA, Perl A (2008) Haplotypes of the HRES-1 endogenous retrovirus are associated with development and disease manifestations of systemic lupus erythematosus. Arthritis Rheum 58:532–540

    Article  PubMed  CAS  Google Scholar 

  67. Perl A, Colombo E, Dai H et al (1995) Antibody reactivity to the HRES-1 endogenous retroviral element identifies a subset of patients with systemic lupus erythematosus and overlap syndromes. Correlation with antinuclear antibodies and HLA class II alleles. Arthritis Rheum 38:1660–1671

    Article  PubMed  CAS  Google Scholar 

  68. Nagy G, Ward J, Mosser DD et al (2006) Regulation of CD4 expression via recycling by HRES-1/RAB4 controls susceptibility to HIV infection. J Biol Chem 281:34574–34591

    Article  PubMed  CAS  Google Scholar 

  69. Fernandez DR, Telarico T, Bonilla E et al (2009) Activation of mammalian target of rapamycin controls the loss of TCRzeta in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation. J Immunol 182:2063–2073

    Article  PubMed  CAS  Google Scholar 

  70. Adelman MK, Marchalonis JJ (2002) Endogenous retroviruses in systemic lupus erythematosus: candidate lupus viruses. Clin Immunol 102:107–116

    Article  PubMed  CAS  Google Scholar 

  71. Chambers AE, Banerjee S, Chaplin T et al (2003) Histone acetylation-mediated regulation of genes in leukaemic cells. Eur J Cancer 39:1165–1175

    Article  PubMed  CAS  Google Scholar 

  72. Zabel MD, Weis JJ, Weis JH (1999) Lymphoid transcription of the murine CD21 gene is positively regulated by histone acetylation. J Immunol 163:2697–2703

    PubMed  CAS  Google Scholar 

  73. Seo JS, Cho NY, Kim HR et al (2008) Cell cycle arrest and lytic induction of EBV-transformed B lymphoblastoid cells by a histone deacetylase inhibitor, Trichostatin A. Oncol Rep 19:93–98

    PubMed  CAS  Google Scholar 

  74. Mishra N, Reilly CM, Brown DR, Ruiz P, Gilkeson GS (2003) Histone deacetylase inhibitors modulate renal disease in the MRL-lpr/lpr mouse. J Clin Invest 111:539–552

    PubMed  CAS  Google Scholar 

  75. Xiao C, Srinivasan L, Calado DP et al (2008) Lymphoproliferative disease and autoimmunity in mice with increased miR-17–92 expression in lymphocytes. Nat Immunol 9:405–414

    Article  PubMed  CAS  Google Scholar 

  76. Park BL, Kim LH, Shin HD, Park YW, Uhm WS, Bae SC (2004) Association analyses of DNA methyltransferase-1 (DNMT1) polymorphisms with systemic lupus erythematosus. J Hum Genet 49:642–646

    Article  PubMed  CAS  Google Scholar 

  77. Gorelik G, Fang JY, Wu A, Sawalha AH, Richardson B (2007) Impaired T cell protein kinase C delta activation decreases ERK pathway signaling in idiopathic and hydralazine-induced lupus. J Immunol 179:5553–5563

    PubMed  CAS  Google Scholar 

  78. Miyamoto A, Nakayama K, Imaki H et al (2002) Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cdelta. Nature 416:865–869

    Article  PubMed  CAS  Google Scholar 

  79. Jury EC, Isenberg DA, Mauri C, Ehrenstein MR (2006) Atorvastatin restores Lck expression and lipid raft-associated signaling in T cells from patients with systemic lupus erythematosus. J Immunol 177:7416–7422

    PubMed  CAS  Google Scholar 

  80. Oelke K, Lu Q, Richardson D et al (2004) Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors. Arthritis Rheum 50:1850–1860

    Article  PubMed  CAS  Google Scholar 

  81. Nagumo H, Agematsu K (1998) Synergistic augmentative effect of interleukin-10 and CD27/CD70 interactions on B-cell immunoglobulin synthesis. Immunology 94:388–394

    Article  PubMed  CAS  Google Scholar 

  82. Liang B, Gardner DB, Griswold DE, Bugelski PJ, Song XY (2006) Anti-interleukin-6 monoclonal antibody inhibits autoimmune responses in a murine model of systemic lupus erythematosus. Immunology 119:296–305

    Article  PubMed  CAS  Google Scholar 

  83. Tang LP, Cho CH, Hui WM et al (2006) An inverse correlation between Interleukin-6 and select gene promoter methylation in patients with gastric cancer. Digestion 74:85–90

    Article  PubMed  CAS  Google Scholar 

  84. Hillion S, Garaud S, Devauchelle V et al (2007) Interleukin-6 is responsible for aberrant B-cell receptor-mediated regulation of RAG expression in systemic lupus erythematosus. Immunology 122:371–380

    Article  PubMed  CAS  Google Scholar 

  85. Hu N, Qiu X, Luo Y et al (2008) Abnormal histone modification patterns in lupus CD4+ T cells. J Rheumatol 35:804–810

    PubMed  CAS  Google Scholar 

  86. Lei W, Luo Y, Yan K et al (2009) Abnormal DNA methylation in CD4+ T cells from patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis. Scand J Rheumatol 14:1–6

    Google Scholar 

  87. Huber LC, Brock M, Hemmatazad H et al (2007) Histone deacetylase/acetylase activity in total synovial tissue derived from rheumatoid arthritis and osteoarthritis patients. Arthritis Rheum 56:1087–1093

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

Thanks are due to Dr. WH Brooks (Moffitt Research Institute, Tampa, USA) for editorial assistance. We are also grateful to Cindy Séné and Simone Forest for their secretarial help.

Author information

Authors and Affiliations

  1. EA2216 Immunology and Pathology, IFR 148 ScInBioS, Université de Brest, Université Européenne de Bretagne, Brest, France

    Yves Renaudineau, Soizic Garaud, Christelle Le Dantec, Ruby Alonso-Ramirez, Capucine Daridon & Pierre Youinou

  2. Experimental Immunotherapy Department, Center for Molecular Immunology, Havana, Cuba

    Ruby Alonso-Ramirez

  3. Laboratory of Immunology, CHU Brest, Hôpital Morvan, Brest, France

    Yves Renaudineau, Capucine Daridon & Pierre Youinou

  4. Laboratory of Immunology, Brest University Medical School Hospital, BP824, 29609, Brest, France

    Yves Renaudineau

Authors
  1. Yves Renaudineau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Soizic Garaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christelle Le Dantec
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ruby Alonso-Ramirez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Capucine Daridon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pierre Youinou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yves Renaudineau.

Additional information

This work was supported by grants from the Conseil Regional de Bretagne, the Conseil Général du Finistère, and the French Ministry for Education and Research.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Renaudineau, Y., Garaud, S., Le Dantec, C. et al. Autoreactive B Cells and Epigenetics. Clinic Rev Allerg Immunol 39, 85–94 (2010). https://doi.org/10.1007/s12016-009-8174-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-009-8174-6

Keywords

Search

Navigation