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Objective  Fcγ receptor  II b (Fcγ RII b) is an essential negative regulator of B cells that blocks B cell receptor ( BCR ) signaling and triggers c‐Abl–dependent apoptosis of B cells. Fcγ RII b‐deficient mice display splenomegaly with expansion of B cells, leading to lupus. Fcγ RII b‐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 Fcγ RII b‐I232T polymorphism, we investigated the role of Fcγ RII b in the deletion of low‐affinity germinal center ( GC ) B cells, an important mechanism for preventing autoimmunity.    Methods  We generated Fcγ RII b 232T/T  mice to mimic human Fcγ RII b‐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.    Results  Compared to wild‐type ( WT ) mice, Fcγ RII b 232T/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  V H  186.2 genes encoding high‐affinity  BCR  was reduced. Notably, Fcγ RII b 232T/T  mice had a higher number of  GC  light zone B cells and showed less apoptosis than  WT  mice, despite having equivalent follicular helper T cell numbers and function. Moreover, phosphorylation of c‐Abl was reduced in Fcγ RII b 232T/T  mice, and treatment of  WT  mice with the c‐Abl inhibitor nilotinib during the peak of  GC  response resulted in reduced affinity maturation reminiscent of Fcγ RII b 232T/T  mice.    Conclusion  Our findings provide evidence of a critical role of Fcγ RII b/c‐Abl in the negative selection of  GC  B cells in Fcγ RII b 232T/T  mice. Importantly, our findings indicate potential benefits of up‐regulating Fcγ RII b expression in B cells for treatment of systemic lupus erythematosus.

arthritis and rheumatology

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