Store-operated Calcium Entry into B Cells Regulates Autoimmune Inflammation.

Store-operated Calcium Entry into B Cells Regulates Autoimmune Inflammation. Yakugaku Zasshi. 2016;136(3):473-8 Authors: Baba Y 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 e...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research