Orai3 and orai1 mediate crac channel function and metabolic reprogramming in b cells

Scott M. Emrich, Ryan E. Yoast, Xuexin Zhang, Adam J. Fike, Yin Hu Wang, Kristen N. Bricker, Anthony Y. Tao, Ping Xin, Vonn Walter, Martin T. Johnson, Trayambak Pathak, Adam C. Straub, Stefan Feske, Ziaur S.M. Rahman, Mohamed Trebak

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 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, 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 effector functions of B lymphocytes.

Original languageEnglish (US)
Article numbere84708
JournaleLife
Volume12
DOIs
StatePublished - Feb 2023

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

Cite this