title: Mcl-1 is essential for the survival of plasma cells.
abstract: The long-term survival of plasma cells is entirely dependent on signals derived from their environment. These extrinsic factors presumably induce and sustain the expression of antiapoptotic proteins of the Bcl-2 family. It is uncertain whether there is specificity among Bcl-2 family members in the survival of plasma cells and whether their expression is linked to specific extrinsic factors. We found here that deletion of the gene encoding the antiapoptotic protein Mcl-1 in plasma cells resulted in rapid depletion of this population in vivo. Furthermore, we found that the receptor BCMA was needed to establish high expression of Mcl-1 in bone marrow but not spleen plasma cells and that establishing this survival pathway preceded the component of plasma cell differentiation that depends on the transcriptional repressor Blimp-1. Our results identify a critical role for Mcl-1 in the maintenance of plasma cells.
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors: Victor
authors: V
authors: Peperzak
authors: Ingela
authors: I
authors: Vikström
authors: Jennifer
authors: J
authors: Walker
authors: Stefan P
authors: SP
authors: Glaser
authors: Melanie
authors: M
authors: LePage
authors: Christine M
authors: CM
authors: Coquery
authors: Loren D
authors: LD
authors: Erickson
authors: Kirsten
authors: K
authors: Fairfax
authors: Fabienne
authors: F
authors: Mackay
authors: Andreas
authors: A
authors: Strasser
authors: Stephen L
authors: SL
authors: Nutt
authors: David M
authors: DM
authors: Tarlinton
mesh_terms: D000818:Animals; D053301:B-Cell Maturation Antigen / Q000378:metabolism*; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010950:Plasma Cells / Q000166:cytology / Q000502:physiology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D053301:B-Cell Maturation Antigen; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; C513258:Prdm1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; C490176:Tnfrsf17 protein, mouse; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1
references: Nat Med. 2003 Sep;9(9):1131-7
references: 12925846
references: J Immunol. 2003 Nov 15;171(10):4969-73
references: 14607890
references: Cell Cycle. 2004 Oct;3(10):1259-62
references: 15467463
references: J Immunol. 2011 Jun 1;186(11):6136-47
references: 21536804
references: Genes Dev. 2012 Jan 15;26(2):120-5
references: 22279045
references: Nat Commun. 2011 Sep 06;2:465
references: 21897376
references: J Immunol. 2009 Feb 15;182(4):2113-23
references: 19201864
references: Blood. 2004 Apr 15;103(8):3148-57
references: 15070697
references: Eur J Immunol. 1988 Feb;18(2):313-6
references: 3350037
references: Annu Rev Immunol. 2005;23:367-86
references: 15771575
references: J Exp Med. 2000 Sep 18;192(6):813-21
references: 10993912
references: Immunol Rev. 2010 Sep;237(1):140-59
references: 20727034
references: Science. 2010 Nov 19;330(6007):1095-9
references: 20929728
references: J Immunol. 1999 Oct 15;163(8):4192-8
references: 10510355
references: Immunity. 2004 Jun;20(6):707-18
references: 15189736
references: J Immunol. 2009 Jan 15;182(2):890-901
references: 19124732
references: Blood. 2008 Mar 1;111(5):2755-64
references: 18180376
references: Br J Haematol. 2004 May;125(3):373-82
references: 15086420
references: Arthritis Rheum. 2011 Jul;63(7):1793-803
references: 21452293
references: Trends Immunol. 2011 Dec;32(12):595-602
references: 22001488
references: J Exp Med. 2006 Nov 27;203(12):2683-90
references: 17101733
references: Nat Rev Immunol. 2006 Oct;6(10):741-50
references: 16977339
references: Leukemia. 2005 Jul;19(7):1248-52
references: 15902294
references: Immunol Rev. 2003 Aug;194:177-95
references: 12846815
references: Nature. 1996 Jun 27;381(6585):751-8
references: 8657279
references: Nature. 1994 Mar 24;368(6469):339-42
references: 8127368
references: Nature. 2008 Jul 10;454(7201):226-31
references: 18568025
references: Immunity. 2007 May;26(5):555-66
references: 17509907
references: Arthritis Rheum. 2011 Jul;63(7):1782-92
references: 21452294
references: Eur J Immunol. 1996 Feb;26(2):444-8
references: 8617316
references: Blood. 2012 Jun 14;119(24):5807-16
references: 22538851
references: J Exp Med. 2011 Jul 4;208(7):1435-46
references: 21690252
references: Nat Rev Immunol. 2006 Oct;6(10):785-90
references: 16998511
references: J Exp Med. 2004 Jan 5;199(1):91-8
references: 14707116
references: J Immunol. 2008 Mar 15;180(6):3655-9
references: 18322170
references: N Engl J Med. 2007 Nov 8;357(19):1903-15
references: 17989383
references: Nat Immunol. 2011 Feb;12(2):151-9
references: 21217761
references: Nature. 1991 Apr 4;350(6317):423-6
references: 1901381
references: Blood. 2004 Jan 15;103(2):689-94
references: 14512299
references: J Clin Invest. 2008 Aug;118(8):2887-95
references: 18618015
references: Immunity. 2002 Jul;17(1):51-62
references: 12150891
references: Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10967-71
references: 20534453
references: Immunity. 2006 Aug;25(2):225-36
references: 16919487
references: J Immunol. 2003 Aug 15;171(4):1684-90
references: 12902466
references: J Immunol. 2010 Dec 15;185(12):7180-5
references: 21068399
references: Semin Immunol. 2006 Oct;18(5):305-17
references: 16916610
references: Immunity. 2003 Oct;19(4):607-20
references: 14563324
references: Curr Opin Immunol. 2008 Apr;20(2):162-9
references: 18456483
references: J Exp Med. 2004 Oct 18;200(8):967-77
references: 15492122
references: Immunity. 1997 Mar;6(3):303-13
references: 9075931