title: Influence of interleukin-2 deficiency on the generation of autoimmune B cells.
abstract: The production of auto-antibodies is one of the predominant characteristics of autoimmune disorders. Because IL-2 deficient mice develop autoimmunity, we asked how IL-2 deficiency might impair endogenous mechanisms of B cell tolerance. To this end, we mated BALB/c anti-dsDNA H chain knock-in mice, in which B cells producing anti-dsDNA antibodies are properly regulated, with IL-2 deficient mice and assessed the phenotype of their offspring. IL-2 deficient mice expressing the anti-dsDNA H chain knock-in allele developed anti-dsDNA antibodies of both IgM and IgG isotypes. Production of these antibodies occurred through the disruption of several mechanisms of endogenous tolerance, including deletion, maturational arrest, and follicular exclusion. In summary, our results suggest that IL-2 plays an important role in regulating B cell tolerance.
authors: Division of Transplantation, University of Nebraska Medical Center, 983285 Nebraska Medical Center, Omaha, NE 68198-3285, USA.
authors: Lucile E
authors: LE
authors: Wrenshall
authors: Deandra R
authors: DR
authors: Smith
authors: Elliot T
authors: ET
authors: Stevens
authors: John D
authors: JD
authors: Miller
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000276:immunology; D017209:Apoptosis; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018925:Chemokines / Q000302:isolation & purification / Q000378:metabolism; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D000974:Antibodies, Antinuclear; D018925:Chemokines; D007376:Interleukin-2
references: J Exp Med. 1992 Nov 1;176(5):1477-82
references: 1402691
references: Nature. 1991 Aug 15;352(6336):621-4
references: 1830926
references: Immunity. 1995 Oct;3(4):521-30
references: 7584142
references: Immunity. 1997 Jan;6(1):97-105
references: 9052841
references: Lupus. 1999;8(1):29-38
references: 10025597
references: Annu Rev Immunol. 2005;23:127-59
references: 15771568
references: Immunol Rev. 2005 Apr;204:165-83
references: 15790358
references: J Immunol. 2005 Apr 15;174(8):4821-7
references: 15814708
references: J Immunol. 2005 Jul 1;175(1):104-11
references: 15972636
references: J Immunol. 2005 Oct 1;175(7):4255-64
references: 16177065
references: Autoimmun Rev. 2006 Feb;5(2):118-21
references: 16431340
references: Blood. 2006 Aug 1;108(3):974-82
references: 16861350
references: Autoimmun Rev. 2006 Jul;5(6):403-8
references: 16890894
references: J Autoimmun. 2006 Aug;27(1):50-3
references: 16904870
references: Immunity. 2006 Dec;25(6):989-1001
references: 17112751
references: J Autoimmun. 2006 Dec;27(4):289-96
references: 17207605
references: J Autoimmun. 2007 Mar-May;28(2-3):143-51
references: 17363215
references: J Autoimmun. 2007 Mar-May;28(2-3):152-9
references: 17368846
references: Curr Opin Immunol. 2007 Jun;19(3):327-36
references: 17433868
references: J Immunol. 2000 Feb 1;164(3):1161-8
references: 10640726
references: Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12694-9
references: 11070085
references: J Immunol. 2001 Aug 15;167(4):1886-90
references: 11489967
references: Immunology. 2001 Oct;104(2):127-34
references: 11683951
references: J Immunol. 2002 Jan 1;168(1):13-21
references: 11751941
references: J Exp Med. 2002 Jan 21;195(2):181-8
references: 11805145
references: Immunity. 2002 Apr;16(4):535-46
references: 11970877
references: J Exp Med. 2002 Dec 16;196(12):1543-52
references: 12486097
references: J Exp Med. 2003 Aug 4;198(3):505-12
references: 12900524
references: J Immunol. 2004 Apr 15;172(8):4700-8
references: 15067045
references: Nat Immunol. 2004 Jul;5(7):713-20
references: 15184895
references: Science. 1990 Dec 21;250(4988):1720-3
references: 2125367
references: Science. 1995 Jun 9;268(5216):1472-6
references: 7770771