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Nat Commun. 2019 Apr 29;10(1):1970. doi: 10.1038/s41467-019-09434-0.

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

Author information

1
The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 OXY, England, UK. marion.espeli@inserm.fr.
2
UMR996 - Inflammation, Chemokines and Immunopathology, Inserm, Univ Paris-Sud, Université Paris-Saclay, Clamart, F-92140, France. marion.espeli@inserm.fr.
3
The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 OXY, England, UK.
4
Wellcome Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK.
5
Cambridge Institute of Therapeutic Immunology & Infectious Disease, ​Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, University of Cambridge, CB2 0AW, Cambridge, UK.
6
UMR996 - Inflammation, Chemokines and Immunopathology, Inserm, Univ Paris-Sud, Université Paris-Saclay, Clamart, F-92140, France.
7
Lymphocyte Signalling and Development, Babraham Institute, CB22 3AT, Cambridge, UK.
8
The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 OXY, England, UK. kgcs2@cam.ac.uk.
9
Cambridge Institute of Therapeutic Immunology & Infectious Disease, ​Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, University of Cambridge, CB2 0AW, Cambridge, UK. kgcs2@cam.ac.uk.

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.

PMID:
31036800
PMCID:
PMC6488660
DOI:
10.1038/s41467-019-09434-0
[Indexed for MEDLINE]
Free PMC Article

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