title: Transcription factor Mef2c is required for B cell proliferation and survival after antigen receptor stimulation.
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-x(L). Our results emphasize an unrecognized but critical function for Mef2c in BCR signaling.
authors.affiliation: Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Wilker
authors.forename: Masako
authors.initials: M
authors.lastname: Kohyama
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Sandau
authors.forename: Jörn C
authors.initials: JC
authors.lastname: Albring
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagawa
authors.forename: John J
authors.initials: JJ
authors.lastname: Schwarz
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: 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
chemical_list: D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D018006:Myogenic Regulatory Factors; D011947:Receptors, Antigen, B-Cell; D014157:Transcription Factors; D019703:Calcineurin