Repository logo

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

Published version

Change log


Espeli, Marion 
Bashford-Rogers, Rachael  ORCID logo
Sowerby, John 
Alouche, Nagham 


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. Its impact on specific B cell tolerance checkpoints is unknown. Here we show that reduced expression of FcγRIIb leads to increased deletion and anergy of autoreactive immature B cells, but despite this autoreactive B cells expand in the germinal center and serum autoantibodies are produced, even in response to exogenous non-self antigen. Thus, we show FcγRIIb has opposing effects on pre- and post-immune tolerance checkpoints, and suggest B cell tolerance requires the control of “bystander” germinal center B cells with low or no affinity for the immunization antigen.



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

Journal Title

Nature Communications

Conference Name

Journal ISSN


Volume Title



Nature Publishing Group
Lupus Research Institute's (LRI) (unknown)
Wellcome Trust (083650/Z/07/Z)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0514-10109)
Wellcome Trust (200871/Z/16/Z)
Wellcome Trust (106068/Z/14/Z)
This work was funded by the Wellcome Trust (Programme Grant Number 083650/Z/07/Z to KGCS) and supported by the NIHR Cambridge Biomedical Research Centre. ME was funded by the Wellcome Trust (Programme Grant Number 083650/Z/07/Z), by a Junior Team Leader starting grant from the Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LabEx LERMIT) supported by a grant from ANR (ANR-10-LABX-33) under the program “Investissements d'Avenir” (ANR-11-IDEX-0003-01) and by an ANR @RAction starting grant (ANR-14-ACHN- 0008). KGCS is an NIHR Senior Clinical Investigator and a Distinguished Innovator of the Lupus Research Institute.