Calcium signaling in B cells: Regulation of cytosolic Ca2+ increase and its sensor molecules, STIM1 and STIM2

Calcium signals are crucial for diverse cellular functions including adhesion, differentiation, proliferation, effector functions and gene expression. After engagement of the B cell receptor, the intracellular calcium ion (Ca2+) concentration is increased promoting the activation of various signaling cascades. While elevated Ca2+ in the cytosol initially comes from the endoplasmic reticulum (ER), a continuous influx of extracellular Ca2+ is required to maintain the increased level of cytosolic Ca2+. Store-operated Ca2+ entry manages this process, which is regulated by an ER calcium sensor, stromal interaction molecule (STIM). STIM proteins sense changes in the levels of Ca2+ stored within the ER lumen and regulates the Ca2+-release activated Ca2+ channel in the plasma membrane. This review focuses on the signaling pathways leading to Ca2+ influx and the role of Ca2+ signals in B cell functions.