口腔1
细胞生物学
NFAT公司
生物
刺激1
转录因子
内质网
基因
生物化学
作者
Scott M. Emrich,Ryan E. Yoast,Xuexin Zhang,Adam J Fike,Yin‐Hu Wang,Kristen N Bricker,Anthony Tao,Ping Xin,Vonn Walter,Martin Johnson,Trayambak Pathak,Adam C. Straub,Stefan Feske,Ziaur S. M. Rahman,Mohamed Trebak
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2023-02-21
卷期号:12
被引量:7
摘要
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.
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