B Cell Receptor Signaling

Baba, Yoshihiro, Kurosaki, Tomohiro, Yoshihiro Baba, Tomohiro Kurosaki

Increase in intracellular levels of calcium ions (Ca(2+)) is one of the key triggering signals for the development of B cell response to the antigen. The diverse Ca(2+) signals finely controlled by multiple factors participate in the regulation of gene expression, B cell development, and effector functions. B cell receptor (BCR)-initiated Ca(2+) mobilization is sourced from two pathways: one is the release of Ca(2+) from the intracellular stores, endoplasmic reticulum (ER), and other is the prolonged influx of extracellular Ca(2+) induced by depleting the stores via store-operated calcium entry (SOCE) and calcium release-activated calcium (CRAC) channels. The identification of stromal interaction molecule 1(STIM1 ), the ER Ca(2+) sensor, and Orai1 , a key subunit of the CRAC channel pore, has now provided the tools to understand the mode of Ca(2+) influx regulation and physiological relevance. Herein, we discuss our current understanding of the molecular mechanisms underlying BCR-triggered Ca(2+) signaling as well as its contribution to the B cell biological processes and diseases.