Ca(2+) signaling in antigen receptor-activated B lymphocytes.

B cells respond to antigen stimulation with mobilization of the Ca(2+) second messenger in two phases operated by two distinct sets of effector proteins. First, an antigen receptor-specific Ca(2+) initiation complex is assembled, activated, and targeted to the plasma membrane to trigger the transient release of Ca(2+) from intracellular stores of the endoplasmic reticulum. Second, more ubiquitously expressed Ca(2+) channels of the plasma membrane are opened to allow for sustained Ca(2+) influx from the extracellular medium. Depending on the developmental stage of the B cell, the kinetics and profile of the two phases are adjusted at multiple levels of positive and negative regulation. A molecular basis for the Ca(2+) signaling plasticity is provided by cytosolic and transmembrane adapter proteins. They act as signal organizers, which control enzyme/substrate interactions by directing the different signaling modules into specific subcellular compartments. These arrangements orchestrate a graduated activation of Ca(2+)-sensitive downstream pathways, which ultimately determine appropriate cellular responses, namely elimination of autoreactive B cells or proliferation and differentiation of immunocompetent B cells into antibody-secreting plasma cells.