title: [Role of STIM-dependent Ca(2+) influx in regulatory B cells].
abstract: B cells positively regulate immune responses through antibody production and effector T cell differentiation. In addition to such protective roles against pathogenesis, B cells also serve as negative regulators of autoimmunity by secreting an anti-inflammatory cytokine, interleukin-10 (IL-10). These B cell functions are caused by encountering their cognate antigens through their B cell receptors (BCR). A central response of BCR stimulation is intracellular Ca(2+) elevation, which is derived mainly from two pathways, Ca(2+) release from endoplasmic reticulum (ER) stores and Ca(2+) influx from the extracellular space across the plasma membrane. Although 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 ER, its physiological role in B cells remains elusive. Stromal interaction molecules (STIM), which consist of STIM1 and its homolog, STIM2, serve as ER calcium sensors and are essential for SOC influx after antigen stimulation. We have recently found that STIM1- and STIM2-induced SOC influx is critical for regulatory B cell function required to limit experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Even through several B cell populations have been reported to suppress inflammation of autoimmune diseases through production of IL-10, which subset of them exerts their regulatory function during EAE is not fully understood. This review focuses on our recent progress in the role of STIM-dependent SOC influx as a key signal for B cell regulatory function and the latest findings for understanding how regulatory B cells suppress the development of EAE.
authors.affiliation: Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Baba
mesh_terms: D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2
chemical_list: D015220:Calcium Channels; D008562:Membrane Glycoproteins; C100757:Stim1 protein, mouse; C525024:Stim2 protein, mouse; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D002118:Calcium