title: MiR-210 is induced by Oct-2, regulates B cells, and inhibits autoantibody production.
abstract: MicroRNAs (MiRs) are small, noncoding RNAs that regulate gene expression posttranscriptionally. In this study, we show that MiR-210 is induced by Oct-2, a key transcriptional mediator of B cell activation. Germline deletion of MiR-210 results in the development of autoantibodies from 5 mo of age. Overexpression of MiR-210 in vivo resulted in cell autonomous expansion of the B1 lineage and impaired fitness of B2 cells. Mice overexpressing MiR-210 exhibited impaired class-switched Ab responses, a finding confirmed in wild-type B cells transfected with a MiR-210 mimic. In vitro studies demonstrated defects in cellular proliferation and cell cycle entry, which were consistent with the transcriptomic analysis demonstrating downregulation of genes involved in cellular proliferation and B cell activation. These findings indicate that Oct-2 induction of MiR-210 provides a novel inhibitory mechanism for the control of B cells and autoantibody production.
authors: Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK.
authors: Yingting
authors: Y
authors: Mok
authors: Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK.
authors: Vera
authors: V
authors: Schwierzeck
authors: Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK.
authors: David C
authors: DC
authors: Thomas
authors: Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, CB22 3AT, UK.
authors: Elena
authors: E
authors: Vigorito
authors: Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK.
authors: Tim F
authors: TF
authors: Rayner
authors: Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK.
authors: Lorna B
authors: LB
authors: Jarvis
authors: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors: Haydn M
authors: HM
authors: Prosser
authors: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors: Allan
authors: A
authors: Bradley
authors: MRC Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham, B15 2TT, UK.
authors: David R
authors: DR
authors: Withers
authors: Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK.
authors: Inga-Lill
authors: IL
authors: Mårtensson
authors: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
authors: Lynn M
authors: LM
authors: Corcoran
authors: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors: Cherie
authors: C
authors: Blenkiron
authors: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors: Eric A
authors: EA
authors: Miska
authors: Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK.
authors: Paul A
authors: PA
authors: Lyons
authors: Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK.
authors: Kenneth G C
authors: KGC
authors: Smith
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002469:Cell Separation; D047369:Chromatin Immunoprecipitation; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis* / Q000276:immunology; D050813:Octamer Transcription Factor-2 / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D001323:Autoantibodies; C549325:MIRN210 microRNA, mouse; D035683:MicroRNAs; D050813:Octamer Transcription Factor-2; C489206:Pou2f2 protein, mouse
references: Methods Mol Biol. 2003;224:149-57
references: 12710672
references: FEBS Lett. 2012 Apr 24;586(8):1201-7
references: 22575656
references: Blood. 2012 Jan 19;119(3):767-76
references: 22117047
references: Br J Haematol. 2008 May;141(5):672-5
references: 18318758
references: J Exp Med. 1985 Jun 1;161(6):1554-68
references: 3874257
references: Nat Immunol. 2001 Jan;2(1):69-74
references: 11135581
references: Nat Rev Immunol. 2008 Jan;8(1):22-33
references: 18097447
references: Curr Opin Immunol. 1995 Jun;7(3):355-9
references: 7546400
references: Nature. 2007 Jun 28;447(7148):1130-4
references: 17554337
references: Nature. 2008 Sep 4;455(7209):64-71
references: 18668037
references: Curr Opin Immunol. 2008 Apr;20(2):149-57
references: 18434123
references: Int Immunol. 1995 Jan;7(1):55-68
references: 7536467
references: Cell. 2008 Mar 7;132(5):860-74
references: 18329371
references: Immunity. 2007 Dec;27(6):847-59
references: 18055230
references: RNA. 2004 Oct;10(10):1507-17
references: 15383676
references: Cell. 2007 Oct 5;131(1):146-59
references: 17923094
references: J Exp Med. 2008 Feb 18;205(2):409-21
references: 18250192
references: Blood. 2011 May 19;117(20):5340-9
references: 21403133
references: Immunity. 1994 Nov;1(8):635-45
references: 7600291
references: Nat Rev Mol Cell Biol. 2009 Feb;10(2):126-39
references: 19165215
references: Immunity. 2010 Nov 24;33(5):713-22
references: 21093320
references: J Exp Med. 2008 Sep 29;205(10):2199-206
references: 18762567
references: Genome Res. 2009 Jan;19(1):92-105
references: 18955434
references: J Immunol. 2002 Jan 1;168(1):9-12
references: 11751940
references: Nat Rev Immunol. 2005 Jun;5(6):497-508
references: 15928681
references: J Exp Med. 1996 Jul 1;184(1):277-81
references: 8691143
references: Bioinformatics. 2002;18 Suppl 1:S96-104
references: 12169536
references: Science. 2007 Apr 27;316(5824):604-8
references: 17463289
references: Immunity. 2010 Jun 25;32(6):828-39
references: 20605486
references: Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11550-4
references: 1722338
references: J Biomed Inform. 2011 Oct;44(5):839-47
references: 21605702
references: Nature. 2010 Aug 12;466(7308):835-40
references: 20703300
references: Nat Biotechnol. 2011 Aug 07;29(9):840-5
references: 21822254
references: J Biol Chem. 2008 Jun 6;283(23):15878-83
references: 18417479
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D149-53
references: 18158296
references: Annu Rev Immunol. 2002;20:253-300
references: 11861604
references: Mol Cell. 2007 Jun 8;26(5):745-52
references: 17540599
references: Immunity. 2008 May;28(5):621-9
references: 18450484
references: Nature. 2008 Sep 4;455(7209):58-63
references: 18668040
references: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
references: 16199517
references: J Exp Med. 2008 Apr 14;205(4):883-95
references: 18362174
references: Cell Mol Immunol. 2013 Mar;10(2):107-12
references: 23314697
references: Cell. 2009 Jan 23;136(2):215-33
references: 19167326
references: Curr Top Microbiol Immunol. 1990;166:175-81
references: 2073796
references: Eur J Immunol. 1998 Mar;28(3):1040-51
references: 9541600
references: J Pathol. 2011 Jun;224(2):280-8
references: 21465485
references: Br J Haematol. 2008 Sep;142(5):732-44
references: 18537969
references: Immunity. 2008 May;28(5):630-8
references: 18455451
references: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W486-91
references: 16845056
references: Mol Cell. 2009 Sep 24;35(6):856-67
references: 19782034
references: J Immunol. 1997 Dec 1;159(11):5273-84
references: 9548466
references: Genome Biol. 2007;8(10):R214
references: 17922911
references: Stat Appl Genet Mol Biol. 2004;3:Article3
references: 16646809
references: J Exp Med. 2012 Oct 22;209(11):2049-64
references: 23045607
references: Cell. 2006 Sep 22;126(6):1203-17
references: 16990141
references: Science. 2008 Aug 1;321(5889):696-9
references: 18566249
references: PLoS Genet. 2012;8(7):e1002797
references: 22844244