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

作者：Bhattacharyya Sankar; Deb Jolly; Patra Amiya K; Duong Anh Thuy Pham; Chen Wen; Vaeth Martin; Berberich Siebelt Friederike; Klein Hessling Stefan; Lamperti Edward D; Reifenberg Kurt; Jellusova Julia; Schweizer Astrid; Nitschke Lars; Leich Ellen; Rosenwald Andreas; Brunner Cornelia; Engelmann Swen; Bommhardt Ursula; Avots Andris; Mueller Martin R; Kondo Eisaku; Serfling Edgar^*

来源：Journal of Experimental Medicine, 2011, 208(4): 823-839.

DOI：10.1084/jem.20100945

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/alpha A, 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 IgG31(+) plasmablast formation. Mice bearing NFATc1(-/-) B cells harbor twofold more interleukin 10-producing B cells. NFATc1(-/-) B cells suppress the synthesis of interferon-gamma 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 Ca(2+) flux and calcineurin (Cn) activation. By affecting CD22, Rcan1, CnA, and NFATc1/alpha A expression, NFATc1 controls the Ca(2+)-dependent Cn-NFAT signaling network and, thereby, the fate of splenic B cells upon BCR stimulation.

• 出版日期2011-4-11
• 单位河北医科大学