Article abstract
Nature Immunology 9, 603 - 612 (2008)
Published online: 27 April 2008 | Corrected online: 8 May 2008 | doi:10.1038/ni.1609
Transcription factor Mef2c is required for B cell proliferation and survival after antigen receptor stimulation
Peter R Wilker1, Masako Kohyama1, Michelle M Sandau1, Jörn C Albring1, Osamu Nakagawa2, John J Schwarz3 & Kenneth M Murphy1,4
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.
- Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
- Department of Molecular Biology and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
- Center for Cardiovascular Sciences, Albany Medical Center, Albany, New York 12208, USA.
- Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Correspondence to: Kenneth M Murphy1,4 e-mail: kmurphy@pathology.wustl.edu
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