1. Orai3 and Orai1 mediate CRAC channel function and metabolic reprogramming in B cells.
- Author
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Emrich, Scott M., Yoast, Ryan E., Xuexin Zhang, Fike, Adam J., Yin-Hu Wang, Bricker, Kristen N., Tao, Anthony Y., Ping Xin, Walter, Vonn, Johnson, Martin T., Pathak, Trayambak, Straub, Adam C., Feske, Stefan, Rahman, Ziaur S. M., and Trebak, Mohamed
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B cells , *HUMORAL immunity , *T cells , *IMMUNE response , *VIRUS diseases , *CELL physiology - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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