 Store-operated calcium entry, SOS, is essential for B cell activation and antibody production. Two OII proteins, ORI1 and ORI3, are required for this process. However, the exact mechanism by which these proteins facilitate SOS remains unclear. This study demonstrates that both ORI1 and ORI3 are necessary for SOS in B cells, as well as for the activation of NFAT and metabolism. Additionally, the authors found that the simultaneous deletion of both ORI1 and ORI3 does not affect humoral immunity, indicating that other co-stimulatory signals can compensate for the lack of CIC channel activity. This article was authored by Scott M. Emeridge, Ryan E. Yoast, Shui-Shin Zhong, and others.