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A p38 MAPK-MEF2C pathway regulates B-cell proliferation

Dustin Khiem1, Jason G Cyster, John J Schwarz

  • 1Cardiovascular Research Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158-2517, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 29, 2008
PubMed

B lymphocytes are an integral part of the adaptive immune system. On antigen binding to the B-cell receptor (BCR), B cells rapidly proliferate and differentiate into antibody-secreting plasma cells. The p38 mitogen-activated protein kinase (MAPK) pathway functions downstream of the BCR to control cell proliferation, but the transcriptional effectors of this pathway in B cells have remained elusive. In the present study, we inactivated Mef2c exclusively in B cells by conditional gene targeting in mice. Loss of MEF2C function resulted in a reduced immune response to antigen, defective germinal center formation, and a severe defect in B-cell proliferation, and we show that MEF2C regulates proliferation in response to BCR stimulation via the p38 MAPK pathway. p38 directly phosphorylates MEF2C via three residues in the C-terminal transactivation domain, establishing MEF2C as a direct transcriptional effector of BCR signaling via p38 MAPK.

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