Transcription factor Mef2c is required for B cell proliferation and survival after antigen receptor stimulation.
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-x(L). Our results emphasize an unrecognized but critical function for Mef2c in BCR signaling.
Wilker
Peter R
PR
Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Kohyama
Masako
M
Sandau
Michelle M
MM
Albring
Jörn C
JC
Nakagawa
Osamu
O
Schwarz
John J
JJ
Murphy
Kenneth M
KM
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D019703:Calcineurin / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D064326:MEF2 Transcription Factors; D051379:Mice; D018006:Myogenic Regulatory Factors / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology
D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D018006:Myogenic Regulatory Factors; D011947:Receptors, Antigen, B-Cell; D014157:Transcription Factors; D019703:Calcineurin