TY - JOUR
T1 - NFATc1 affects mouse splenic B cell function by controlling the calcineurin–NFAT signaling network
AU - Bhattacharyya, Sankar
AU - Deb, Jolly
AU - Patra, Amiya K.
AU - Thuy, Pham DA
AU - Chen, Wen
AU - Vaeth, Martin
AU - Berberich-Siebelt, Friederike
AU - Klein-Hessling, Stefan
AU - Lamperti, Edward D.
AU - Reifenberg, Kurt
AU - Jellusova, Julia
AU - Schweizer, Astrid
AU - Nitschke, Lars
AU - Leich, Ellen
AU - Rosenwald, Andreas
AU - Brunner, Cornelia
AU - Engelmann, Swen
AU - Bommhardt, Ursula
AU - Avots, Andris
AU - Müller, Martin R.
AU - Kondo, Eisaku
AU - Serfling, Edgar
PY - 2011/4/11
Y1 - 2011/4/11
N2 - 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.
AB - 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.
U2 - 10.1084/jem.20100945
DO - 10.1084/jem.20100945
M3 - Article
SN - 0022-1007
VL - 208
SP - 823
EP - 839
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -
