The Lupus-Associated Fcγ Receptor IIb-I232T Polymorphism Results in Impairment in the Negative Selection of Low-Affinity Germinal Center B Cells Via c-Abl in Mice.

Arthritis & Rheumatology
Jyun-Pei JhouShiang-Jong Tzeng

Abstract

Fcγ receptor IIb (FcγRIIb) is an essential negative regulator of B cells that blocks B cell receptor (BCR) signaling and triggers c-Abl-dependent apoptosis of B cells. FcγRIIb-deficient mice display splenomegaly with expansion of B cells, leading to lupus. FcγRIIb-I232T is a hypofunctional polymorphism associated with lupus susceptibility in humans, an autoimmune disease linked to diminished deletion of autoreactive B cells. In the context of the FcγRIIb-I232T polymorphism, we investigated the role of FcγRIIb in the deletion of low-affinity germinal center (GC) B cells, an important mechanism for preventing autoimmunity. We generated FcγRIIb232T/T mice to mimic human FcγRIIb-I232T carriers and immunized mice with chicken gamma globulin (CGG)-conjugated NP, a T cell-dependent antigen, to examine the response of GC B cells. Compared to wild-type (WT) mice, FcγRIIb232T/T mice showed increased numbers of low-affinity NP-specific IgG and NP-specific B cells and plasma cells; additionally, the expression of a somatic mutation (W33L) in their VH 186.2 genes encoding high-affinity BCR was reduced. Notably, FcγRIIb232T/T mice had a higher number of GC light zone B cells and showed less apoptosis than WT mice, despite having equivalent f...Continue Reading

References

Jun 1, 1986·Immunological Reviews·I C MacLennan, D Gray
Jan 1, 1994·Annual Review of Immunology·I C MacLennan
Mar 5, 1996·Proceedings of the National Academy of Sciences of the United States of America·S K RayB Diamond
Jul 14, 1999·Immunity·R N PearseJ V Ravetch
Aug 3, 1999·The Journal of Experimental Medicine·Y TakahashiG Kelsoe
Jun 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·D QinJ G Tew
Dec 13, 2003·Immunity·Gregory A VigliantiAnn Marshak-Rothstein
Aug 24, 2005·The Journal of Biological Chemistry·Shiang-Jong TzengSusan K Pierce
Aug 23, 2006·The Journal of Experimental Medicine·Meggan MackayBetty Diamond
Dec 5, 2006·Journal of Clinical and Experimental Hematopathology : JCEH·Hito-Aki SaitohMitsunori Yamakawa
Feb 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kaihong SuRobert P Kimberly
Apr 17, 2007·Proceedings of the National Academy of Sciences of the United States of America·Menna R ClatworthyKenneth G C Smith
Mar 26, 2008·The Journal of Experimental Medicine·Rebecca J BrownlieKenneth G C Smith
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Apr 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lisa C WillcocksKenneth G C Smith
May 5, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chelsey L GoinsJoshy Jacob
Nov 17, 2010·The Journal of Experimental Medicine·Thomas TillerHedda Wardemann
Dec 29, 2010·Proceedings of the National Academy of Sciences of the United States of America·Michael WaisbergSilvia Bolland
Sep 25, 2012·Nature Immunology·David Dominguez-SolaRiccardo Dalla-Favera
Nov 9, 2012·European Journal of Immunology·Wai-Hang LeungSilvia Bolland
Jul 28, 2013·Science·Ziv ShulmanGabriel D Victora
May 9, 2014·Nature·Alexander D GitlinMichel C Nussenzweig
Jul 22, 2014·Nature Immunology·Andrew PinceticJeffrey V Ravetch
Feb 7, 2015·Nature Reviews. Immunology·Nilushi S De Silva, Ulf Klein
Oct 18, 2015·Journal of Biomedical Science·Shiang-Jong TzengHui-Ying Wang
Dec 20, 2015·Immunological Reviews·Marion EspéliMenna R Clatworthy

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Methods Mentioned

BETA
gene knockout
ELISA
PCR
flow cytometry

Software Mentioned

GraphPad Prism
SAMtools

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