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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Change history
08 May 2008
In the version of this article initially published online, Figure 7c is incorrect. The error has been corrected for all versions of the article.
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Acknowledgements
Supported by the Howard Hughes Medical Institute (K.M.M.) and the National Institutes of Health (5P01AI031238 and 5T32HL007317).
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P.R.W. designed experiments, did research, analyzed and interpreted results, and wrote the manuscript; M.K. did immunohistochemistry; M.M.S. sorted B cell subsets and did Mef2c expression analysis; J.C.A. contributed gene expression microarray data for some mouse tissues; O.N. provided spleens from Srpk3-deficient mice; J.J.S. provided mice with a loxP-flanked Mef2c allele; and K.M.M. directed the study and wrote the manuscript.
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Wilker, P., Kohyama, M., Sandau, M. et al. Transcription factor Mef2c is required for B cell proliferation and survival after antigen receptor stimulation. Nat Immunol 9, 603–612 (2008). https://doi.org/10.1038/ni.1609
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DOI: https://doi.org/10.1038/ni.1609
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