Store-operated Calcium Entry into B Cells Regulates Autoimmune Inflammation

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  • Baba Yoshihiro
    Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center (IFReC), Osaka University

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  • B細胞ストア作動性カルシウム流入による自己免疫性炎症反応の制御機構
  • Symposium Review B細胞ストア作動性カルシウム流入による自己免疫性炎症反応の制御機構
  • Symposium Review B サイボウ ストア サドウセイ カルシウム リュウニュウ ニ ヨル ジコ メンエキセイ エンショウ ハンノウ ノ セイギョ キコウ

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  Alterations in the cytosolic concentration of calcium ions (Ca2+) are important signals for various physiological events. The engagement of B cell receptors (BCR) results in the transient release of Ca2+ into cytosol from endoplasmic reticulum (ER) stores. In turn, this decrease in ER luminal Ca2+ concentration triggers the opening of Ca2+ channels in the plasma membrane, inducing a sustained influx of extracellular Ca2+ into cells. These processes are referred to as store-operated Ca2+ entry (SOCE), which is an essential pathway for continuous Ca2+ 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.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 136 (3), 473-478, 2016-03-01

    The Pharmaceutical Society of Japan

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