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

Peter R. Wilker, Masako Kohyama, Michelle M. Sandau, Jörn C. Albring, Osamu Nakagawa, John J. Schwarz, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

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.

Original languageEnglish
Pages (from-to)603-612
Number of pages10
JournalNature immunology
Volume9
Issue number6
DOIs
StatePublished - Jun 1 2008

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