ORCID
- Patra, Amiya: 0000-0002-5297-809X
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
First Page
823
Last Page
839
ISSN
0022-1007
Organisational Unit
Peninsula Medical School
Recommended Citation
Bhattacharyya, S., Deb, J., Patra, A., Thuy, P., Chen, W., Vaeth, M., Berberich-Siebelt, F., Klein-Hessling, S., Lamperti, E., Reifenberg, K., Jellusova, J., Schweizer, A., Nitschke, L., Leich, E., Rosenwald, A., Brunner, C., Engelmann, S., Bommhardt, U., Avots, A., Müller, M., Kondo, E., & Serfling, E. (2011) 'NFATc1 affects mouse splenic B cell function by controlling the calcineurin–NFAT signaling network', Journal of Experimental Medicine, 208(4), pp. 823-839. Available at: https://doi.org/10.1084/jem.20100945
