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

Nature Immunology volume 9, pages 603612 (2008) | Download Citation

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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).

Author information

Affiliations

  1. Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

    • Peter R Wilker
    • , Masako Kohyama
    • , Michelle M Sandau
    • , Jörn C Albring
    •  & Kenneth M Murphy
  2. Department of Molecular Biology and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

    • Osamu Nakagawa
  3. Center for Cardiovascular Sciences, Albany Medical Center, Albany, New York 12208, USA.

    • John J Schwarz
  4. Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

    • Kenneth M Murphy

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Contributions

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.

Corresponding author

Correspondence to Kenneth M Murphy.

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https://doi.org/10.1038/ni.1609

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