PMID: 15383609Sep 24, 2004Paper

A critical role for Fc gamma RIIB in the induction of rheumatoid factors

The Journal of Immunology : Official Journal of the American Association of Immunologists
Thomas MollS Izui

Abstract

Rheumatoid factors (RF) are autoantibodies with specificity for the Fc portion of IgG, and IgG-containing immune complexes are likely to be the major source of RF autoantigens. Therefore, the activation of RF-producing B cells could be controlled specifically through recognition of IgG immune complexes by the low-affinity IgG FcR, FcgammaRIIB, a potent negative regulator of the BCR. To test this possibility, we determined the development of RF in C57BL/6 (B6) mice lacking FcgammaRIIB, in relation to the H2 haplotype, complement C3, and the Y-linked autoimmune acceleration (Yaa) mutation. FcgammaRIIB-null B6 mice displayed substantial anti-IgG2a RF activities in their sera, in addition to anti-DNA autoantibodies. Their RF and anti-DNA responses were linked to the H2(b) haplotype, but were suppressed almost completely by the H2(d) haplotype. Strikingly, the absence of C3 failed to modulate RF production, but strongly inhibited anti-DNA production. Furthermore, we observed that partial FcgammaRIIB deficiency (i.e., heterozygous level of FcgammaRIIB expression) was sufficient to induce the production of RF and anti-DNA autoantibodies in the presence of the Yaa mutation. In contrast to FcgammaRIIB, the deficiency in another BCR nega...Continue Reading

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Citations

Jul 5, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Peter BorossJ Sjef Verbeek
Feb 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shuichi KikuchiShozo Izui
Sep 18, 2009·Annals of the New York Academy of Sciences·Valli De ReVito Racanelli
Feb 16, 2006·The Journal of Experimental Medicine·Stefka B PetkovaDerry C Roopenian
Nov 26, 2008·Immunology and Cell Biology·Geoffrey A PieterszP Mark Hogarth
Aug 7, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kristian Hannestad, Helge Scott
Jan 7, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shuichi KikuchiShozo Izui
Jun 3, 2009·Immunology and Cell Biology·Kalina A NikolovaTchavdar L Vassilev
Mar 7, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fei F ShihPaul M Allen

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