Transcription factor Mef2c is required for B cell proliferation and survival after antigen receptor stimulation

PR Wilker, M Kohyama, MM Sandau, JC Albring… - Nature …, 2008 - nature.com
PR Wilker, M Kohyama, MM Sandau, JC Albring, O Nakagawa, JJ Schwarz, KM Murphy
Nature immunology, 2008nature.com
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 …
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-xL. Our results emphasize an unrecognized but critical function for Mef2c in BCR signaling.
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