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- Title
Transcription factor Mef2c is required for B cell proliferation and survival after antigen receptor stimulation.
- Authors
Wilker, Peter R; Kohyama, Masako; Sandau, Michelle M; Albring, Jörn C; Nakagawa, Osamu; Schwarz, John J; Murphy, Kenneth M
- Abstract
Calcineurin is required for B cell receptor (BCR)-induced proliferation of mature B cells. Paradoxically, loss of NFAT transcription factors, themselves calcineurin targets, induces hyperactivity, which suggests that calcineurin targets other than NFAT are required for BCR-induced proliferation. Here we demonstrate a function for the calcineurin-regulated transcription factor Mef2c in B cells. BCR-induced calcium mobilization was intact after Mef2c deletion, but loss of Mef2c caused defects in B cell proliferation and survival after BCR stimulation in vitro and lower T cell-dependent antibody responses and germinal center formation in vivo. Mef2c activity was specific to BCR stimulation, as Toll-like receptor and CD40 signaling induced normal responses in Mef2c-deficient B cells. Mef2c-dependent targets included the genes encoding cyclin D2 and the prosurvival factor Bcl-x(L). Our results emphasize an unrecognized but critical function for Mef2c in BCR signaling.
- Publication
Nature immunology, 2008, Vol 9, Issue 6, p603
- ISSN
1529-2916
- Publication type
Journal Article
- DOI
10.1038/ni.1609