ORCID

Abstract

By studying mice in which the Nfatc1 gene was inactivated in bone marrow, spleen, or germinal center B cells, we show that NFATc1 supports the proliferation and suppresses the activation-induced cell death of splenic B cells upon B cell receptor (BCR) stimulation. BCR triggering leads to expression of NFATc1/αA, a short isoform of NFATc1, in splenic B cells. NFATc1 ablation impaired Ig class switch to IgG3 induced by T cell–independent type II antigens, as well as IgG3+ plasmablast formation. Mice bearing NFATc1−/− B cells harbor twofold more interleukin 10–producing B cells. NFATc1−/− B cells suppress the synthesis of interferon-γ by T cells in vitro, and these mice exhibit a mild clinical course of experimental autoimmune encephalomyelitis. In large part, the defective functions of NFATc1−/− B cells are caused by decreased BCR-induced Ca2+ flux and calcineurin (Cn) activation. By affecting CD22, Rcan1, CnA, and NFATc1/αA expression, NFATc1 controls the Ca2+-dependent Cn–NFAT signaling network and, thereby, the fate of splenic B cells upon BCR stimulation.

DOI

10.1084/jem.20100945

Publication Date

2011-04-11

Publication Title

Journal of Experimental Medicine

Volume

208

Issue

4

ISSN

0022-1007

Organisational Unit

Peninsula Medical School

First Page

823

Last Page

839

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