title: Vitamin A-dependent transcriptional activation of the nuclear factor of activated T cells c1 (NFATc1) is critical for the development and survival of B1 cells.
abstract: B1 cells represent a distinct subset of B cells that produce most of the natural serum IgM and much of the gut IgA and function as an important component of early immune responses to pathogens. The development of B1 cells depends on the nuclear factor of activated T cells c1 (NFATc1), a transcription factor abundantly expressed by B1 cells but not by conventional B2 cells. However, the factors that regulate the expression of NFATc1 in B1 cells remain unknown. Here we show that a vitamin A-deficient diet results in reduction of NFATc1 expression in B1 cells and almost complete loss of the B1 cell compartment. As a consequence, vitamin A-deficient mice have reduced serum IgM and are unable to mount T cell-independent antibody responses against bacterial antigens. We demonstrate that injection of all-trans retinoic acid induces the expression of NFATc1, particularly from the constitutive P2 promoter, and leads to the increase of the B1 cells. Thus, the retinoic acid-dependent pathway is critical for regulating NFATc1 expression and for maintenance of the natural memory B cell compartment.
authors.affiliation: Laboratory for Mucosal Immunity, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Mikako
authors.initials: M
authors.lastname: Maruya
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hanae
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Michio
authors.initials: M
authors.lastname: Miyajima
authors.forename: Osami
authors.initials: O
authors.lastname: Kanagawa
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Wakayama
authors.forename: Sidonia
authors.initials: S
authors.lastname: Fagarasan
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014801:Vitamin A / Q000378:metabolism*
chemical_list: D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D018168:Receptors, Retinoic Acid; D014801:Vitamin A