FcγRIIb differentially regulates pre-immune and germinal center B cell tolerance in mouse and human

Marion Espéli (), Rachael Bashford-Rogers, John M. Sowerby, Nagham Alouche, Limy Wong, Alice E. Denton, Michelle A. Linterman and Kenneth G. C. Smith ()
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Marion Espéli: University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus
Rachael Bashford-Rogers: University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus
John M. Sowerby: University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus
Nagham Alouche: Univ Paris-Sud, Université Paris-Saclay
Limy Wong: University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus
Alice E. Denton: University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus
Michelle A. Linterman: University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus
Kenneth G. C. Smith: University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Several tolerance checkpoints exist throughout B cell development to control autoreactive B cells and prevent the generation of pathogenic autoantibodies. FcγRIIb is an Fc receptor that inhibits B cell activation and, if defective, is associated with autoimmune disease, yet its impact on specific B cell tolerance checkpoints is unknown. Here we show that reduced expression of FcγRIIb enhances the deletion and anergy of autoreactive immature B cells, but in contrast promotes autoreactive B cell expansion in the germinal center and serum autoantibody production, even in response to exogenous, non-self antigens. Our data thus show that FcγRIIb has opposing effects on pre-immune and post-immune tolerance checkpoints, and suggest that B cell tolerance requires the control of bystander germinal center B cells with low or no affinity for the immunizing antigen.

Date: 2019
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DOI: 10.1038/s41467-019-09434-0

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