NFATc1 affects mouse splenic B cell function by controlling the calcineurin–NFAT signaling network

• DOI: 10.1084/jem.20100945
• Publication Date: 2011-04-05T03:18:28Z
• Authors: Sankar Bhattacharyya; Jolly Deb; Amiya K. Patra; Duong Anh Thuy Pham; Wen Chen; Martin Vaeth; Friederike Berber...; Stefan Klein-Hess...; Edward D. Lamperti; Kurt Reifenberg; Julia Jellusova; Astrid Schweizer; Lars Nitschke; Ellen Leich; Andreas Rosenwald; Cornelia Brunner; Swen Engelmann; Ursula Bommhardt; Andris Avots; Martin R. Müller; Eisaku Kondo; Edgar Serfling
• Keywords: 0301 basic medicine; B-Lymphocytes; NFATC Transcription Factors; Calcineurin; T-Lymphocytes; Receptors, Antigen, B-Cell; Lymphocyte Activation; Immunoglobulin Class Switching; Article; Mice; 03 medical and health sciences; Animals; Calcium; Spleen; Signal Transduction

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.