title: The calcium sensors STIM1 and STIM2 control B cell regulatory function through interleukin-10 production.
abstract: A chief Ca(2+) entry pathway in immune cells is store-operated Ca(2+) (SOC) influx, which is triggered by depletion of Ca(2+) from the endoplasmic reticulum (ER). However, its physiological role in B cells remains elusive. Here, we show that ER calcium sensors STIM1- and STIM2-induced SOC influx is critical for B cell regulatory function. B cell-specific deletion of STIM1 and STIM2 in mice caused a profound defect in B cell receptor (BCR)-induced SOC influx and proliferation. However, B cell development and antibody responses were unaffected. Remarkably, B cells lacking both STIM proteins failed to produce the anti-inflammatory cytokine IL-10 because of defective activation of nuclear factor of activated T cells (NFAT) after BCR stimulation. This resulted in exacerbation of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Our data establish STIM-dependent SOC influx as a key signal for B cell regulatory function required to limit autoimmunity.
authors.affiliation: Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fujii
authors.forename: Akemi
authors.initials: A
authors.lastname: Baba
authors.forename: Masaki
authors.initials: M
authors.lastname: Hikida
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Baba
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001927:Brain Diseases / Q000276:immunology / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D049109:Cell Proliferation; D002470:Cell Survival; D004660:Encephalitis; D050031:Hashimoto Disease / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D050778:NFATC Transcription Factors / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2
chemical_list: D015220:Calcium Channels; D008562:Membrane Glycoproteins; D050778:NFATC Transcription Factors; D011947:Receptors, Antigen, B-Cell; C100757:Stim1 protein, mouse; C525024:Stim2 protein, mouse; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D016753:Interleukin-10; D002118:Calcium