Store-operated calcium entry into B cells regulates autoimmune inflammation

研究成果: ジャーナルへの寄稿総説査読

1 被引用数 (Scopus)


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.

ジャーナルYakugaku Zasshi
出版ステータス出版済み - 3月 1 2016

!!!All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬科学


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