Epigenetics of peripheral B-cell differentiation and the antibody response

Frontiers in Immunology

Volumn 6, Issue DEC, 2015, Pages

  Zan, Hong ^a   Casali, Paolo ^a  

^a Mays Cancer Center at UT Health San Antonio   (United States)

Author keywords

AID; B cell; Blimp 1; Class switch DNA recombination; Epigenetics; Histone post translational modification; Memory B cell; MicroRNA; Plasma cell differentiation; Somatic hypermutation

Indexed keywords

B LYMPHOCYTE INDUCED MATURATION PROTEIN 1; MICRORNA; MICRORNA 155; MICRORNA 361; PROTEIN BCL 6; UNCLASSIFIED DRUG;

3' UNTRANSLATED REGION; ANTIBODY PRODUCTION; ANTIBODY RESPONSE; AUTOIMMUNITY; B LYMPHOCYTE; CELL DIFFERENTIATION; DNA METHYLATION; DNA MODIFICATION; DOWN REGULATION; EPIGENETICS; GENE EXPRESSION; HISTONE MODIFICATION; HUMAN; INTESTINE FLORA; PHENOTYPE; PLASMA CELL; PROTEIN PROCESSING; REVIEW; UPREGULATION;

EID: 84954213361     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2015.00631     Document Type: Review

References (187)

1. Hedrich CM, Tsokos GC. Epigenetic mechanisms in systemic lupus erythematosus and other autoimmune diseases. Trends Mol Med (2011) 17:714-24. doi:10.1016/j.molmed.2011.07.005.
2. Xu Z, Zan H, Pone EJ, Mai T, Casali P. Immunoglobulin class-switch DNA recombination: induction, targeting and beyond. Nat Rev Immunol (2012) 12:517-31. doi:10.1038/nri3216.
3. Zan H, Casali P. Regulation of Aicda expression and AID activity. Autoimmunity (2013) 46:81-99. doi:10.3109/08916934.2012.749244.
4. Li G, Zan H, Xu Z, Casali P. Epigenetics of the antibody response. Trends Immunol (2013) 34:460-70. doi:10.1016/j.it.2013.03.006.
5. De Silva NS, Klein U. Dynamics of B cells in germinal centres. Nat Rev Immunol (2015) 15:137-48. doi:10.1038/nri3804.
6. Nutt SL, Hodgkin PD, Tarlinton DM, Corcoran LM. The generation of antibody-secreting plasma cells. Nat Rev Immunol (2015) 15:160-71. doi:10.1038/nri3795.
7. Kurosaki T, Kometani K, Ise W. Memory B cells. Nat Rev Immunol (2015) 15:149-59. doi:10.1038/nri3802.
8. Li G, Pone EJ, Lan T, Tran DC, Mai T, Zan H, et al. Combinatorial H3K9acS10ph histone modification in IgH locus S regions targets 14-3-3 adaptors and AID to specify antibody class-switch DNA recombination. Cell Rep (2013) 5:702-14. doi:10.1016/j.celrep.2013.09.031.
9. Zan H, Tat C, Casali P. microRNAs in lupus. Autoimmunity (2014) 47:272-85. doi:10.3109/08916934.2014.915955.
10. White CA, Pone EJ, Lam T, Tat C, Hayama KL, Li G, et al. Histone deacetylase inhibitors upregulate B cell microRNAs that silence AID and Blimp-1 expression for epigenetic modulation of antibody and autoantibody responses. J Immunol (2014) 193:5933-50. doi:10.4049/jimmunol.1401702.
11. Shaknovich R, Cerchietti L, Tsikitas L, Kormaksson M, De S, Figueroa ME, et al. DNA methyltransferase 1 and DNA methylation patterning contribute to germinal center B-cell differentiation. Blood (2011) 118:3559-69. doi:10.1182/blood-2011-06-357996.
12. Chowdhury M, Forouhi O, Dayal S, McCloskey N, Gould HJ, Felsenfeld G, et al. Analysis of intergenic transcription and histone modification across the human immunoglobulin heavy-chain locus. Proc Natl Acad Sci U S A (2008) 105:15872-7. doi:10.1073/pnas.0808462105.
13. Jeevan-Raj BP, Robert I, Heyer V, Page A, Wang JH, Cammas F, et al. Epigenetic tethering of AID to the donor switch region during immunoglobulin class switch recombination. J Exp Med (2011) 208:1649-60. doi:10.1084/jem.20110118.
14. Robbiani DF, 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. doi:10.1016/j.cell.2008.09.062.
15. Pasqualucci L, Bhagat G, Jankovic M, Compagno M, Smith P, Muramatsu M, et al. AID is required for germinal center-derived lymphomagenesis. Nat Genet (2008) 40:108-12. doi:10.1038/ng.2007.35.
16. Robbiani DF, Bunting S, Feldhahn N, Bothmer A, Camps J, Deroubaix S, et al. AID produces DNA double-strand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations. Mol Cell (2009) 36:631-41. doi:10.1016/j.molcel.2009.11.007.
17. Hasham MG, Donghia NM, Coffey E, Maynard J, Snow KJ, Ames J, et al. Widespread genomic breaks generated by activation-induced cytidine deaminase are prevented by homologous recombination. Nat Immunol (2010) 11:820-6. doi:10.1038/ni.1909.
18. Chandra V, Bortnick A, Murre C. AID targeting: old mysteries and new challenges. Trends Immunol (2015) 36(9):527-35. doi:10.1016/j.it.2015.07.003.
19. Park SR, Zan H, Pal Z, Zhang J, Al-Qahtani A, Pone EJ, et al. HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation. Nat Immunol (2009) 10:540-50. doi:10.1038/ni.1725.
20. White CA, Seth Hawkins J, Pone EJ, Yu ES, Al-Qahtani A, Mai T, et al. AID dysregulation in lupus-prone MRL/Fas(lpr/lpr) mice increases class switch DNA recombination and promotes interchromosomal c-Myc/IgH loci translocations: modulation by HoxC4. Autoimmunity (2011) 44:585-98. doi:10.3109/08916934.2011.577128.
21. Fujimura S, Matsui T, Kuwahara K, Maeda K, Sakaguchi N. Germinal center B-cell-associated DNA hypomethylation at transcriptional regions of the AID gene. Mol Immunol (2008) 45:1712-9. doi:10.1016/j.molimm.2007.09.023.
22. Crouch EE, Li Z, Takizawa M, Fichtner-Feigl S, Gourzi P, Montano C, et al. Regulation of AID expression in the immune response. J Exp Med (2007) 204:1145-56. doi:10.1084/jem.20061952.
23. Begum NA, Stanlie A, Nakata M, Akiyama H, Honjo T. The histone chaperone Spt6 is required for activation-induced cytidine deaminase target determination through H3K4me3 regulation. J Biol Chem (2012) 287:32415-29. doi:10.1074/jbc.M112.351569.
24. Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol (2014) 15:509-24. doi:10.1038/nrm3838.
25. Hausser J, Zavolan M. Identification and consequences of miRNA-target interactions-beyond repression of gene expression. Nat Rev Genet (2014) 15:599-612. doi:10.1038/nrg3765.
26. Cech TR, Steitz JA. The noncoding RNA revolution-trashing old rules to forge new ones. Cell (2014) 157:77-94. doi:10.1016/j.cell.2014.03.008.
27. Malumbres R, Sarosiek KA, Cubedo E, Ruiz JW, Jiang X, Gascoyne RD, et al. Differentiation stage-specific expression of microRNAs in B lymphocytes and diffuse large B-cell lymphomas. Blood (2009) 113:3754-64. doi:10.1182/blood-2008-10-184077.
28. Zhang J, Jima DD, Jacobs C, Fischer R, Gottwein E, Huang G, et al. Patterns of microRNA expression characterize stages of human B-cell differentiation. Blood (2009) 113:4586-94. doi:10.1182/blood-2008-09-178186.
29. Xu S, Guo K, Zeng Q, Huo J, Lam KP. The RNase III enzyme Dicer is essential for germinal center B-cell formation. Blood (2012) 119:767-76. doi:10.1182/blood-2011-05-355412.
30. Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, et al. Regulation of the germinal center response by microRNA-155. Science (2007) 316:604-8. doi:10.1126/science.1141229.
31. Gururajan M, Haga CL, Das S, Leu CM, Hodson D, Josson S, et al. microRNA 125b inhibition of B cell differentiation in germinal centers. Int Immunol (2010) 22:583-92. doi:10.1093/intimm/dxq042.
32. Vigorito E, Perks KL, Abreu-Goodger C, Bunting S, Xiang Z, Kohlhaas S, et al. microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity (2007) 27:847-59. doi:10.1016/j.immuni.2007.10.009.
33. Teng G, Hakimpour P, Landgraf P, Rice A, Tuschl T, Casellas R, et al. microRNA-155 is a negative regulator of activation-induced cytidine deaminase. Immunity (2008) 28:621-9. doi:10.1016/j.immuni.2008.03.015.
34. Dorsett Y, McBride KM, Jankovic M, Gazumyan A, Thai TH, Robbiani DF, et al. microRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation. Immunity (2008) 28:630-8. doi:10.1016/j.immuni.2008.04.002.
35. de Yebenes VG, Belver L, Pisano DG, Gonzalez S, Villasante A, Croce C, et al. miR-181b negatively regulates activation-induced cytidine deaminase in B cells. J Exp Med (2008) 205:2199-206. doi:10.1084/jem.20080579.
36. Borchert GM, Holton NW, Larson ED. Repression of human activation induced cytidine deaminase by miR-93 and miR-155. BMC Cancer (2011) 11:347. doi:10.1186/1471-2407-11-347.
37. Basso K, Schneider C, Shen Q, Holmes AB, Setty M, Leslie C, et al. BCL6 positively regulates AID and germinal center gene expression via repression of miR-155. J Exp Med (2012) 209:2455-65. doi:10.1084/jem.20121387.
38. Faraoni I, Antonetti FR, Cardone J, Bonmassar E. miR-155 gene: a typical multifunctional microRNA. Biochim Biophys Acta (2009) 1792:497-505. doi:10.1016/j.bbadis.2009.02.013.
39. Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, et al. Requirement of bic/microRNA-155 for normal immune function. Science (2007) 316:608-11. doi:10.1126/science.1139253.
40. Thai TH, Patterson HC, Pham DH, Kis-Toth K, Kaminski DA, Tsokos GC. Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in the Fas(lpr) mouse. Proc Natl Acad Sci U S A (2013) 110:20194-9. doi:10.1073/pnas.1317632110.
41. Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell (2007) 129:1401-14. doi:10.1016/j.cell.2007.04.040.
42. Stavnezer J. Complex regulation and function of activation-induced cytidine deaminase. Trends Immunol (2011) 32:194-201. doi:10.1016/j.it.2011.03.003.
43. Kluiver J, van den Berg A, de Jong D, Blokzijl T, Harms G, Bouwman E, et al. Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma. Oncogene (2007) 26:3769-76. doi:10.1038/sj.onc.1210147.
44. Fear DJ, McCloskey N, O'Connor B, Felsenfeld G, Gould HJ. Transcription of Ig germline genes in single human B cells and the role of cytokines in isotype determination. J Immunol (2004) 173:4529-38. doi:10.4049/jimmunol.173.7.4529.
45. Nambu Y, Sugai M, Gonda H, Lee CG, Katakai T, Agata Y, et al. Transcription-coupled events associating with immunoglobulin switch region chromatin. Science (2003) 302:2137-40. doi:10.1126/science.1092481.
46. Wang L, Wuerffel R, Feldman S, Khamlichi AA, Kenter AL. S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination. J Exp Med (2009) 206:1817-30. doi:10.1084/jem.20081678.
47. Daniel JA, Santos MA, Wang Z, Zang C, Schwab KR, Jankovic M, et al. PTIP promotes chromatin changes critical for immunoglobulin class switch recombination. Science (2010) 329:917-23. doi:10.1126/science.1187942.
48. Stanlie A, Aida M, Muramatsu M, Honjo T, Begum NA. Histone3 lysine4 trimethylation regulated by the facilitates chromatin transcription complex is critical for DNA cleavage in class switch recombination. Proc Natl Acad Sci U S A (2010) 107:22190-5. doi:10.1073/pnas.1016923108.
49. Kuang FL, Luo Z, Scharff MD. H3 trimethyl K9 and H3 acetyl K9 chromatin modifications are associated with class switch recombination. Proc Natl Acad Sci U S A (2009) 106:5288-93. doi:10.1073/pnas.0901368106.
50. Rajagopal D, Maul RW, Ghosh A, Chakraborty T, Khamlichi AA, Sen R, et al. Immunoglobulin switch mu sequence causes RNA polymerase II accumulation and reduces dA hypermutation. J Exp Med (2009) 206:1237-44. doi:10.1084/jem.20082514.
51. Pavri R, Gazumyan A, Jankovic M, Di Virgilio M, Klein I, Ansarah-Sobrinho C, et al. Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. Cell (2010) 143:122-33. doi:10.1016/j.cell.2010.09.017.
52. Storck S, Aoufouchi S, Weill JC, Reynaud CA. AID and partners: for better and (not) for worse. Curr Opin Immunol (2011) 23:337-44. doi:10.1016/j.coi.2011.02.002.
53. Kenter AL. AID targeting is dependent on RNA polymerase II pausing. Semin Immunol (2012) 24:281-6. doi:10.1016/j.smim.2012.06.001.
54. Xu Z, Fulop Z, Wu G, Pone EJ, Zhang J, Mai T, et al. 14-3-3 adaptor proteins recruit AID to 5'-AGCT-3'-rich switch regions for class switch recombination. Nat Struct Mol Biol (2010) 17:1124-35. doi:10.1038/nsmb.1884.
55. Schatz DG, Swanson PC. V(D)J recombination: mechanisms of initiation. Annu Rev Genet (2011) 45:167-202. doi:10.1146/annurev-genet-110410-132552.
56. Aida M, Hamad N, Stanlie A, Begum NA, Honjo T. Accumulation of the FACT complex, as well as histone H3.3, serves as a target marker for somatic hypermutation. Proc Natl Acad Sci U S A (2013) 110:7784-9. doi:10.1073/pnas.1305859110.
57. Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, et al. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet (2008) 40:897-903. doi:10.1038/ng.154.
58. Suganuma T, Workman JL. Signals and combinatorial functions of histone modifications. Annu Rev Biochem (2011) 80:473-99. doi:10.1146/annurev-biochem-061809-175347.
59. Bradley SP, Kaminski DA, Peters AH, Jenuwein T, Stavnezer J. The histone methyltransferase Suv39h1 increases class switch recombination specifically to IgA. J Immunol (2006) 177:1179-88. doi:10.4049/jimmunol.177.2.1179.
60. Zan H, White CA, Thomas LM, Mai T, Li G, Xu Z, et al. Rev1 recruits ung to switch regions and enhances du glycosylation for immunoglobulin class switch DNA recombination. Cell Rep (2012) 2:1220-32. doi:10.1016/j.celrep.2012.09.029.
61. Yamane A, Resch W, Kuo N, Kuchen S, Li Z, Sun HW, et al. Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nat Immunol (2011) 12:62-9. doi:10.1038/ni.1964.
62. Pei H, Wu X, Liu T, Yu K, Jelinek DF, Lou Z. The histone methyltransferase MMSET regulates class switch recombination. J Immunol (2013) 190:756-63. doi:10.4049/jimmunol.1201811.
63. Nagaoka H, Ito S, Muramatsu M, Nakata M, Honjo T. DNA cleavage in immunoglobulin somatic hypermutation depends on de novo protein synthesis but not on uracil DNA glycosylase. Proc Natl Acad Sci U S A (2005) 102:2022-7. doi:10.1073/pnas.0409491102.
64. Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell (2011) 43:904-14. doi:10.1016/j.molcel.2011.08.018.
65. Lee JT. Epigenetic regulation by long noncoding RNAs. Science (2012) 338:1435-9. doi:10.1126/science.1231776.
66. Satpathy AT, Chang HY. Long noncoding RNA in hematopoiesis and immunity. Immunity (2015) 42:792-804. doi:10.1016/j.immuni.2015.05.004.
67. Pefanis E, Wang J, Rothschild G, Lim J, Chao J, Rabadan R, et al. Noncoding RNA transcription targets AID to divergently transcribed loci in B cells. Nature (2014) 514:389-93. doi:10.1038/nature13580.
68. Basu U, Meng FL, Keim C, Grinstein V, Pefanis E, Eccleston J, et al. The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell (2011) 144:353-63. doi:10.1016/j.cell.2011.01.001.
69. Zheng S, Vuong BQ, Vaidyanathan B, Lin JY, Huang FT, Chaudhuri J. Non-coding RNA Generated following Lariat Debranching Mediates Targeting of AID to DNA. Cell (2015) 161:762-73. doi:10.1016/j.cell.2015.03.020.
70. Pefanis E, Wang J, Rothschild G, Lim J, Kazadi D, Sun J, et al. RNA exosome-regulated long non-coding RNA transcription controls super-enhancer activity. Cell (2015) 161:774-89. doi:10.1016/j.cell.2015.04.034.
71. Qian J, Wang Q, Dose M, Pruett N, Kieffer-Kwon KR, Resch W, et al. B cell super-enhancers and regulatory clusters recruit AID tumorigenic activity. Cell (2014) 159:1524-37. doi:10.1016/j.cell.2014.11.013.
72. Odegard VH, Kim ST, Anderson SM, Shlomchik MJ, Schatz DG. Histone modifications associated with somatic hypermutation. Immunity (2005) 23:101-10. doi:10.1016/j.immuni.2005.05.007.
73. Daniel JA, Nussenzweig A. The AID-induced DNA damage response in chromatin. Mol Cell (2013) 50:309-21. doi:10.1016/j.molcel.2013.04.017.
74. Wang Q, Oliveira T, Jankovic M, Silva IT, Hakim O, Yao K, et al. Epigenetic targeting of activation-induced cytidine deaminase. Proc Natl Acad Sci U S A (2014) 111:18667-72. doi:10.1073/pnas.1420575111.
75. Willmann KL, Milosevic S, Pauklin S, Schmitz KM, Rangam G, Simon MT, et al. A role for the RNA pol II-associated PAF complex in AID-induced immune diversification. J Exp Med (2012) 209:2099-111. doi:10.1084/jem.20112145.
76. Meng FL, Du Z, Federation A, Hu J, Wang Q, Kieffer-Kwon KR, et al. Convergent transcription at intragenic super-enhancers targets AID-initiated genomic instability. Cell (2014) 159:1538-48. doi:10.1016/j.cell.2014.11.014.
77. Odegard VH, Schatz DG. Targeting of somatic hypermutation. Nat Rev Immunol (2006) 6:573-83. doi:10.1038/nri1896.
78. Kato L, Begum NA, Burroughs AM, Doi T, Kawai J, Daub CO, et al. Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes. Proc Natl Acad Sci U S A (2012) 109:2479-84. doi:10.1073/pnas.1120791109.
79. Orphanides G, LeRoy G, Chang CH, Luse DS, Reinberg D. FACT, a factor that facilitates transcript elongation through nucleosomes. Cell (1998) 92:105-16. doi:10.1016/S0092-8674(00)80903-4.
80. Belotserkovskaya R, Oh S, Bondarenko VA, Orphanides G, Studitsky VM, Reinberg D. FACT facilitates transcription-dependent nucleosome alteration. Science (2003) 301:1090-3. doi:10.1126/science.1085703.
81. Aida M, Honjo T. FACT and H3.3: new markers for the somatic hypermutation. Cell Cycle (2013) 12:2923-4. doi:10.4161/cc.26178.
82. Borchert GM, Holton NW, Edwards KA, Vogel LA, Larson ED. Histone H2A and H2B are monoubiquitinated at AID-targeted loci. PLoS One (2010) 5:e11641. doi:10.1371/journal.pone.0011641.
83. Kannouche PL, Wing J, Lehmann AR. Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. Mol Cell (2004) 14:491-500. doi:10.1016/S1097-2765(04)00259-X.
84. Fraenkel S, Mostoslavsky R, Novobrantseva TI, Pelanda R, Chaudhuri J, Esposito G, et al. Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin kappa-chain locus. Nat Immunol (2007) 8:715-22. doi:10.1038/ni1476.
85. Woo CJ, Martin A, Scharff MD. Induction of somatic hypermutation is associated with modifications in immunoglobulin variable region chromatin. Immunity (2003) 19:479-89. doi:10.1016/S1074-7613(03)00261-9.
86. Kitao H, Kimura M, Yamamoto K, Seo H, Namikoshi K, Agata Y, et al. Regulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion. Int Immunol (2008) 20:277-84. doi:10.1093/intimm/dxm140.
87. Blagodatski A, Batrak V, Schmidl S, Schoetz U, Caldwell RB, Arakawa H, et al. A cis-acting diversification activator both necessary and sufficient for AID-mediated hypermutation. PLoS Genet (2009) 5:e1000332. doi:10.1371/journal.pgen.1000332.
88. Buerstedde JM, Alinikula J, Arakawa H, McDonald JJ, Schatz DG. Targeting of somatic hypermutation by immunoglobulin enhancer and enhancer-like sequences. PLoS Biol (2014) 12:e1001831. doi:10.1371/journal.pbio.1001831.
89. McHeyzer-Williams M, Okitsu S, Wang N, McHeyzer-Williams L. Molecular programming of B cell memory. Nat Rev Immunol (2012) 12:24-34. doi:10.1038/nri3128.
90. Dogan I, Bertocci B, Vilmont V, Delbos F, Megret J, Storck S, et al. Multiple layers of B cell memory with different effector functions. Nat Immunol (2009) 10:1292-9. doi:10.1038/ni.1814.
91. McHeyzer-Williams LJ, Milpied PJ, Okitsu SL, McHeyzer-Williams MG. Class-switched memory B cells remodel BCRs within secondary germinal centers. Nat Immunol (2015) 16:296-305. doi:10.1038/ni.3095.
92. Shi W, Liao Y, Willis SN, Taubenheim N, Inouye M, Tarlinton DM, et al. Transcriptional profiling of mouse B cell terminal differentiation defines a signature for antibody-secreting plasma cells. Nat Immunol (2015) 16:663-73. doi:10.1038/ni.3154.
93. Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell (2010) 38:576-89. doi:10.1016/j.molcel.2010.05.004.
94. Yu J, Angelin-Duclos C, Greenwood J, Liao J, Calame K. Transcriptional repression by blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase. Mol Cell Biol (2000) 20:2592-603. doi:10.1128/MCB.20.7.2592-2603.2000.
95. Su ST, Ying HY, Chiu YK, Lin FR, Chen MY, Lin KI. Involvement of histone demethylase LSD1 in Blimp-1-mediated gene repression during plasma cell differentiation. Mol Cell Biol (2009) 29:1421-31. doi:10.1128/MCB.01158-08.
96. Gyory I, Wu J, Fejer G, Seto E, Wright KL. PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing. Nat Immunol (2004) 5:299-308. doi:10.1038/ni1046.
97. Lemercier C, Brocard MP, Puvion-Dutilleul F, Kao HY, Albagli O, Khochbin S. Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor. J Biol Chem (2002) 277:22045-52. doi:10.1074/jbc.M201736200.
98. Fujita N, Jaye DL, Geigerman C, Akyildiz A, Mooney MR, Boss JM, et al. MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation. Cell (2004) 119:75-86. doi:10.1016/j.cell.2004.09.014.
99. Shen T, Nasrollahi H, Zan H, Casali P. Genome-wide analysis of B cells reveals selective modulation of microRNAs and mRNAs by histone deacetylase inhibitor. Front Immunol (2015) 6:627. doi:10.3389/fimmu.2015.00627.
100. West JA, Viswanathan SR, Yabuuchi A, Cunniff K, Takeuchi A, Park IH, et al. A role for Lin28 in primordial germ-cell development and germ-cell malignancy. Nature (2009) 460:909-13. doi:10.1038/nature08210.
101. Nie K, Zhang T, Allawi H, Gomez M, Liu Y, Chadburn A, et al. Epigenetic down-regulation of the tumor suppressor gene PRDM1/Blimp-1 in diffuse large B cell lymphomas: a potential role of the microRNA let-7. Am J Pathol (2010) 177:1470-9. doi:10.2353/ajpath.2010.091291.
102. Leucci E, Onnis A, Cocco M, De Falco G, Imperatore F, Giuseppina A, et al. B-cell differentiation in EBV-positive Burkitt lymphoma is impaired at posttranscriptional level by miRNA-altered expression. Int J Cancer (2010) 126:1316-26. doi:10.1002/ijc.24655.
103. Sciammas R, Shaffer AL, Schatz JH, Zhao H, Staudt LM, Singh H. Graded expression of interferon regulatory factor-4 coordinates isotype switching with plasma cell differentiation. Immunity (2006) 25:225-36. doi:10.1016/j.immuni.2006.07.009.
104. Good-Jacobson KL. Regulation of germinal center, B-cell memory, and plasma cell formation by histone modifiers. Front Immunol (2014) 5:596. doi:10.3389/fimmu.2014.00596.
105. Baxter J, Sauer S, Peters A, John R, Williams R, Caparros ML, et al. Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes. EMBO J (2004) 23:4462-72. doi:10.1038/sj.emboj.7600414.
106. Caganova M, Carrisi C, Varano G, Mainoldi F, Zanardi F, Germain PL, et al. Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis. J Clin Invest (2013) 123:5009-22. doi:10.1172/JCI70626.
107. Luckey CJ, Bhattacharya D, Goldrath AW, Weissman IL, Benoist C, Mathis D. Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells. Proc Natl Acad Sci U S A (2006) 103:3304-9. doi:10.1073/pnas.0511137103.
108. Lai AY, Mav D, Shah R, Grimm SA, Phadke D, Hatzi K, et al. DNA methylation profiling in human B cells reveals immune regulatory elements and epigenetic plasticity at Alu elements during B-cell activation. Genome Res (2013) 23:2030-41. doi:10.1101/gr.155473.113.
109. Klein U, Tu Y, Stolovitzky GA, Keller JL, Haddad J Jr, Miljkovic V, et al. Transcriptional analysis of the B cell germinal center reaction. Proc Natl Acad Sci U S A (2003) 100:2639-44. doi:10.1073/pnas.0437996100.
110. Cao Z, Sun X, Icli B, Wara AK, Feinberg MW. Role of Kruppel-like factors in leukocyte development, function, and disease. Blood (2010) 116:4404-14. doi:10.1182/blood-2010-05-285353.
111. Calame K. microRNA-155 function in B Cells. Immunity (2007) 27:825-7. doi:10.1016/j.immuni.2007.11.010.
112. Ranzani V, Rossetti G, Panzeri I, Arrigoni A, Bonnal RJ, Curti S, et al. The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4. Nat Immunol (2015) 16:318-25. doi:10.1038/ni.3093.
113. Gonda H, Sugai M, Nambu Y, Katakai T, Agata Y, Mori KJ, et al. The balance between Pax5 and Id2 activities is the key to AID gene expression. J Exp Med (2003) 198:1427-37. doi:10.1084/jem.20030802.
114. Delcuve GP, Khan DH, Davie JR. Roles of histone deacetylases in epigenetic regulation: emerging paradigms from studies with inhibitors. Clin Epigenetics (2012) 4:5. doi:10.1186/1868-7083-4-5.
115. Reilly CM, Regna N, Mishra N. HDAC inhibition in lupus models. Mol Med (2011) 17:417-25. doi:10.2119/molmed.2011.00055.
116. Gottlicher M, Minucci S, Zhu P, Kramer OH, Schimpf A, Giavara S, et al. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J (2001) 20:6969-78. doi:10.1093/emboj/20.24.6969.
117. Davie JR. Inhibition of histone deacetylase activity by butyrate. J Nutr (2003) 133:2485S-93S.
118. Waibel M, Christiansen AJ, Hibbs ML, Shortt J, Jones SA, Simpson I, et al. Manipulation of B-cell responses with histone deacetylase inhibitors. Nat Commun (2015) 6:6838. doi:10.1038/ncomms7838.
119. Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem (2001) 276:36734-41. doi:10.1074/jbc.M101287200.
120. Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev (2001) 81:1031-64.
121. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature (2013) 504:446-50. doi:10.1038/nature12721.
122. Bantscheff M, Hopf C, Savitski MM, Dittmann A, Grandi P, Michon AM, et al. Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat Biotechnol (2011) 29:255-65. doi:10.1038/nbt.1759.
123. Roger T, Lugrin J, Le Roy D, Goy G, Mombelli M, Koessler T, et al. Histone deacetylase inhibitors impair innate immune responses to toll-like receptor agonists and to infection. Blood (2011) 117:1205-17. doi:10.1182/blood-2010-05-284711.
124. Dowdell KC, Pesnicak L, Hoffmann V, Steadman K, Remaley AT, Cohen JI, et al. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, diminishes lymphoproliferation in the Fas -deficient MRL/lpr(-/-) murine model of autoimmune lymphoproliferative syndrome (ALPS). Exp Hematol (2009) 37:487-94. doi:10.1016/j.exphem.2008.12.002.
125. Villagra A, Cheng F, Wang HW, Suarez I, Glozak M, Maurin M, et al. The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance. Nat Immunol (2009) 10:92-100. doi:10.1038/ni.1673.
126. Akimova T, Beier UH, Liu Y, Wang L, Hancock WW. Histone/protein deacetylases and T-cell immune responses. Blood (2012) 119:2443-51. doi:10.1182/blood-2011-10-292003.
127. Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science (2012) 336:1268-73. doi:10.1126/science.1223490.
128. Ivanov II, Honda K. Intestinal commensal microbes as immune modulators. Cell Host Microbe (2012) 12:496-508. doi:10.1016/j.chom.2012.09.009.
129. Brestoff JR, Artis D. Commensal bacteria at the interface of host metabolism and the immune system. Nat Immunol (2013) 14:676-84. doi:10.1038/ni.2640.
130. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell (2014) 157:121-41. doi:10.1016/j.cell.2014.03.011.
131. Thorburn AN, Macia L, Mackay CR. Diet, metabolites, and "western-lifestyle" inflammatory diseases. Immunity (2014) 40:833-42. doi:10.1016/j.immuni.2014.05.014.
132. Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N, Ngom-Bru C, et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med (2014) 20:159-66. doi:10.1038/nm.3444.
133. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature (2013) 504:451-5. doi:10.1038/nature12726.
134. Cahenzli J, Koller Y, Wyss M, Geuking MB, McCoy KD. Intestinal microbial diversity during early-life colonization shapes long-term IgE levels. Cell Host Microbe (2013) 14:559-70. doi:10.1016/j.chom.2013.10.004.
135. Javierre BM, Fernandez AF, Richter J, Al-Shahrour F, Martin-Subero JI, Rodriguez-Ubreva J, et al. Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res (2010) 20:170-9. doi:10.1101/gr.100289.109.
136. Kauffmann F, Demenais F. Gene-environment interactions in asthma and allergic diseases: challenges and perspectives. J Allergy Clin Immunol (2012) 130:1229-40. doi:10.1016/j.jaci.2012.10.038.
137. Blumenthal MN. Genetic, epigenetic, and environmental factors in asthma and allergy. Ann Allergy Asthma Immunol (2012) 108:69-73. doi:10.1016/j.anai.2011.12.003.
138. Ballestar E. Epigenetic alterations in autoimmune rheumatic diseases. Nat Rev Rheumatol (2011) 7:263-71. doi:10.1038/nrrheum.2011.16.
139. Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol (2010) 28:1057-68. doi:10.1038/nbt.1685.
140. Garaud S, Le Dantec C, Jousse-Joulin S, Hanrotel-Saliou C, Saraux A, Mageed RA, et al. IL-6 modulates CD5 expression in B cells from patients with lupus by regulating DNA methylation. J Immunol (2009) 182:5623-32. doi:10.4049/jimmunol.0802412.
141. Strickland FM, Richardson BC. Epigenetics in human autoimmunity. Autoimmunity (2008) 41:278-86. doi:10.1080/08916930802024616.
142. Mazari L, Ouarzane M, Zouali M. Subversion of B lymphocyte tolerance by hydralazine, a potential mechanism for drug-induced lupus. Proc Natl Acad Sci U S A (2007) 104:6317-22. doi:10.1073/pnas.0610434104.
143. Wu SC, Zhang Y. Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol (2010) 11:607-20. doi:10.1038/nrm2950.
144. lpr/lpr mice display increased AID expression and extensive DNA lesions, comprising deletions and insertions, in the immunoglobulin locus: concurrent upregulation of somatic hypermutation and class switch DNA recombination. Autoimmunity (2009) 42:89-103. doi:10.1080/08916930802629554.
145. Pieterse E, Hofstra J, Berden J, Herrmann M, Dieker J, van der Vlag J. Acetylated histones contribute to the immunostimulatory potential of neutrophil extracellular traps in systemic lupus erythematosus. Clin Exp Immunol (2015) 179:68-74. doi:10.1111/cei.12359.
146. Belver L, de Yébenes VG, Ramiro AR. microRNAs prevent the generation of autoreactive antibodies. Immunity (2010) 33:713-22. doi:10.1016/j.immuni.2010.11.010.
147. Ceribelli A, Satoh M, Chan EK. microRNAs and autoimmunity. Curr Opin Immunol (2012) 24:686-91. doi:10.1016/j.coi.2012.07.011.
148. Dai R, Zhang Y, Khan D, Heid B, Caudell D, Crasta O, et al. Identification of a common lupus disease-associated microRNA expression pattern in three different murine models of lupus. PLoS One (2010) 5:e14302. doi:10.1371/journal.pone.0014302.
149. Forster N, Gallinat S, Jablonska J, Weiss S, Elsässer HP, Lutz W. p300 protein acetyltransferase activity suppresses systemic lupus erythematosus-like autoimmune disease in mice. J Immunol (2007) 178:6941-8. doi:10.4049/jimmunol.178.11.6941.
150. Garchow BG, Bartulos Encinas O, Leung YT, Tsao PY, Eisenberg RA, Caricchio R, et al. Silencing of microRNA-21 in vivo ameliorates autoimmune splenomegaly in lupus mice. EMBO Mol Med (2011) 3:605-15. doi:10.1002/emmm.201100171.
151. Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, et al. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol (2008) 9:405-14. doi:10.1038/ni1575.
152. Esteller M. Epigenetics in cancer. N Engl J Med (2008) 358:1148-59. doi:10.1056/NEJMra072067.
153. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet (2011) 12:861-74. doi:10.1038/nrg3074.
154. Jones PA, Baylin SB. The epigenomics of cancer. Cell (2007) 128:683-92. doi:10.1016/j.cell.2007.01.029.
155. De S, Shaknovich R, Riester M, Elemento O, Geng H, Kormaksson M, et al. Aberration in DNA methylation in B-cell lymphomas has a complex origin and increases with disease severity. PLoS Genet (2013) 9:e1003137. doi:10.1371/journal.pgen.1003137.
156. Leshchenko VV, Kuo PY, Shaknovich R, Yang DT, Gellen T, Petrich A, et al. Genomewide DNA methylation analysis reveals novel targets for drug development in mantle cell lymphoma. Blood (2010) 116:1025-34. doi:10.1182/blood-2009-12-257485.
157. Shaknovich R, Melnick A. Epigenetics and B-cell lymphoma. Curr Opin Hematol (2011) 18:293-9. doi:10.1097/MOH.0b013e32834788cf.
158. Fritz EL, Papavasiliou FN. Cytidine deaminases: AIDing DNA demethylation? Genes Dev (2010) 24:2107-14. doi:10.1101/gad.1963010.
159. Greeve J, Philipsen A, Krause K, Klapper W, Heidorn K, Castle BE, et al. Expression of activation-induced cytidine deaminase in human B-cell non-Hodgkin lymphomas. Blood (2003) 101:3574-80. doi:10.1182/blood-2002-08-2424.
160. Shen L, Song CX, He C, Zhang Y. Mechanism and function of oxidative reversal of DNA and RNA methylation. Annu Rev Biochem (2014) 83:585-614. doi:10.1146/annurev-biochem-060713-035513.
161. Schubeler D. Function and information content of DNA methylation. Nature (2015) 517:321-6. doi:10.1038/nature14192.
162. Huang Y, Rao A. Connections between TET proteins and aberrant DNA modification in cancer. Trends Genet (2014) 30:464-74. doi:10.1016/j.tig.2014.07.005.
163. Cimmino L, Dawlaty MM, Ndiaye-Lobry D, Yap YS, Bakogianni S, Yu Y, et al. TET1 is a tumor suppressor of hematopoietic malignancy. Nat Immunol (2015) 16:653-62. doi:10.1038/ni.3148.
164. Rodriguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat Med (2011) 17:330-9. doi:10.1038/nm.2305.
165. Velichutina I, Shaknovich R, Geng H, Johnson NA, Gascoyne RD, Melnick AM, et al. EZH2-mediated epigenetic silencing in germinal center B cells contributes to proliferation and lymphomagenesis. Blood (2010) 116:5247-55. doi:10.1182/blood-2010-04-280149.
166. Yap DB, Chu J, Berg T, Schapira M, Cheng SW, Moradian A, et al. Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood (2011) 117:2451-9. doi:10.1182/blood-2010-11-321208.
167. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. microRNA expression profiles classify human cancers. Nature (2005) 435:834-8. doi:10.1038/nature03702.
168. Baltimore D, Boldin MP, O'Connell RM, Rao DS, Taganov KD. microRNAs: new regulators of immune cell development and function. Nat Immunol (2008) 9:839-45. doi:10.1038/ni.f.209.
169. Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, et al. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med (2008) 14:1271-7. doi:10.1038/nm.1880.
170. Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ (2010) 17:215-20. doi:10.1038/cdd.2009.69.
171. Klein U, Lia M, Crespo M, Siegel R, Shen Q, Mo T, et al. The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell (2010) 17:28-40. doi:10.1016/j.ccr.2009.11.019.
172. Rosenwald A, Wright G, Wiestner A, Chan WC, Connors JM, Campo E, et al. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell (2003) 3:185-97. doi:10.1016/S1535-6108(03)00028-X.
173. Perlot T, Alt FW. Cis-regulatory elements and epigenetic changes control genomic rearrangements of the IgH locus. Adv Immunol (2008) 99:1-32. doi:10.1016/S0065-2776(08)00601-9.
174. Giambra V, Volpi S, Emelyanov AV, Pflugh D, Bothwell AL, Norio P, et al. Pax5 and linker histone H1 coordinate DNA methylation and histone modifications in the 3' regulatory region of the immunoglobulin heavy chain locus. Mol Cell Biol (2008) 28:6123-33. doi:10.1128/MCB.00233-08.
175. Garrett FE, Emelyanov AV, Sepulveda MA, Flanagan P, Volpi S, Li F, et al. Chromatin architecture near a potential 3' end of the IgH locus involves modular regulation of histone modifications during B-Cell development and in vivo occupancy at CTCF sites. Mol Cell Biol (2005) 25:1511-25. doi:10.1128/MCB.25.4.1511-1525.2005.
176. Wang L, Whang N, Wuerffel R, Kenter AL. AID-dependent histone acetylation is detected in immunoglobulin S regions. J Exp Med (2006) 203:215-26. doi:10.1084/jem.20051774.
177. Pasqualucci L, Dominguez-Sola D, Chiarenza A, Fabbri G, Grunn A, Trifonov V, et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature (2011) 471:189-95. doi:10.1038/nature09730.
178. Xu Y. DNA damage: a trigger of innate immunity but a requirement for adaptive immune homeostasis. Nat Rev Immunol (2006) 6:261-70. doi:10.1038/nri1804.
179. Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet (2010) 42:181-5. doi:10.1038/ng.518.
180. Popovic R, Martinez-Garcia E, Giannopoulou EG, Zhang Q, Zhang Q, Ezponda T, et al. Histone methyltransferase MMSET/NSD2 alters EZH2 binding and reprograms the myeloma epigenome through global and focal changes in H3K36 and H3K27 methylation. PLoS Genet (2014) 10:e1004566. doi:10.1371/journal.pgen.1004566.
181. Pasqualucci L. The genetic basis of diffuse large B-cell lymphoma. Curr Opin Hematol (2013) 20:336-44. doi:10.1097/MOH.0b013e3283623d7f.
182. Chambwe N, Kormaksson M, Geng H, De S, Michor F, Johnson NA, et al. Variability in DNA methylation defines novel epigenetic subgroups of DLBCL associated with different clinical outcomes. Blood (2014) 123:1699-708. doi:10.1182/blood-2013-07-509885.
183. Shaknovich R, Geng H, Johnson NA, Tsikitas L, Cerchietti L, Greally JM, et al. DNA methylation signatures define molecular subtypes of diffuse large B-cell lymphoma. Blood (2010) 116:e81-9. doi:10.1182/blood-2010-05-285320.
184. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A (2005) 102:13944-9. doi:10.1073/pnas.0506654102.
185. Lawrie CH, Soneji S, Marafioti T, Cooper CD, Palazzo S, Paterson JC, et al. microRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. Int J Cancer (2007) 121:1156-61. doi:10.1002/ijc.22800.
186. Jin HY, Oda H, Lai M, Skalsky RL, Bethel K, Shepherd J, et al. microRNA-17~92 plays a causative role in lymphomagenesis by coordinating multiple oncogenic pathways. EMBO J (2013) 32:2377-91. doi:10.1038/emboj.2013.178.
187. Aguda BD, Kim Y, Piper-Hunter MG, Friedman A, Marsh CB. microRNA regulation of a cancer network: consequences of the feedback loops involving miR-17-92, E2F, and Myc. Proc Natl Acad Sci U S A (2008) 105:19678-83. doi:10.1073/pnas.0811166106.