title: [Store-operated Calcium Entry into B Cells Regulates Autoimmune Inflammation].
abstract: Alterations in the cytosolic concentration of calcium ions (Ca(2+)) are important signals for various physiological events. The engagement of B cell receptors (BCR) results in the transient release of Ca(2+) into cytosol from endoplasmic reticulum (ER) stores. In turn, this decrease in ER luminal Ca(2+) concentration triggers the opening of Ca(2+) channels in the plasma membrane, inducing a sustained influx of extracellular Ca(2+) into cells. These processes are referred to as store-operated Ca(2+) entry (SOCE), which is an essential pathway for continuous Ca(2+) signaling. While the ER calcium sensor stromal interaction molecule (STIM) 1 and STIM2 are crucial components for SOCE activation, their physiological roles in B cells are unknown. Here we uncover the physiological function of SOCE in B cells by analyzing mice with B cell-specific deletions of STIM1 and STIM2. Our findings indicate that STIM1 and STIM2 are critical for BCR-induced SOCE, as well as the activation of nuclear factors of activated T cells (NFAT), and the subsequent production of interleukin-10 (IL-10). Although STIM proteins are not essential for B cell development and antibody responses, these molecules are required to suppress experimental autoimmune encephalomyelitis (EAE) via an IL-10-dependent mechanism. Accumulating evidence underscores the importance of IL-10-producing B cells in autoimmunity, although the identity of IL-10-producing B cells with a regulatory function in vivo remains unclear. We addressed this issue and identified plasmablasts as IL-10-producing B cells that can suppress EAE inflammation. Our data established STIM-dependent SOCE as a key signal for the regulatory plasmablasts required to limit autoimmunity.
authors.affiliation: Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center (IFReC), Osaka University.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Baba
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004660:Encephalitis / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D050031:Hashimoto Disease / Q000276:immunology; D006801:Humans; D016753:Interleukin-10; D051379:Mice; D000071737:Stromal Interaction Molecule 1 / Q000502:physiology; D000071738:Stromal Interaction Molecule 2 / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D016753:Interleukin-10; D002118:Calcium