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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.

Original publication

DOI

10.1038/s41467-019-09434-0

Type

Journal article

Journal

Nat Commun

Publication Date

29/04/2019

Volume

10

Keywords

Algorithms, Animals, B-Lymphocytes, Cell Differentiation, Cell Proliferation, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Germinal Center, Humans, Immune Tolerance, Leukocytes, Mononuclear, Male, Mice, Receptors, IgG, Software