TY - JOUR TI - Orai3 and Orai1 mediate CRAC channel function and metabolic reprogramming in B cells AU - Emrich, Scott M AU - Yoast, Ryan E AU - Zhang, Xuexin AU - Fike, Adam J AU - Wang, Yin-Hu AU - Bricker, Kristen N AU - Tao, Anthony Y AU - Xin, Ping AU - Walter, Vonn AU - Johnson, Martin T AU - Pathak, Trayambak AU - Straub, Adam C AU - Feske, Stefan AU - Rahman, Ziaur SM AU - Trebak, Mohamed A2 - Prakriya, Murali A2 - Swartz, Kenton J VL - 12 PY - 2023 DA - 2023/02/21 SP - e84708 C1 - eLife 2023;12:e84708 DO - 10.7554/eLife.84708 UR - https://doi.org/10.7554/eLife.84708 AB - The essential role of store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ (CRAC) channels in T cells is well established. In contrast, the contribution of individual Orai isoforms to SOCE and their downstream signaling functions in B cells are poorly understood. Here, we demonstrate changes in the expression of Orai isoforms in response to B cell activation. We show that both Orai3 and Orai1 mediate native CRAC channels in B cells. The combined loss of Orai1 and Orai3, but not Orai3 alone, impairs SOCE, proliferation and survival, nuclear factor of activated T cells (NFAT) activation, mitochondrial respiration, glycolysis, and the metabolic reprogramming of primary B cells in response to antigenic stimulation. Nevertheless, the combined deletion of Orai1 and Orai3 in B cells did not compromise humoral immunity to influenza A virus infection in mice, suggesting that other in vivo co-stimulatory signals can overcome the requirement of BCR-mediated CRAC channel function in B cells. Our results shed important new light on the physiological roles of Orai1 and Orai3 proteins in SOCE and the effector functions of B lymphocytes. KW - Orai1 KW - Orai3 KW - B cells KW - CRAC channels KW - SOCE KW - metabolism JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -