DIFFERENT PATTERNS OF CALCIUM SIGNALING TRIGGERED THROUGH 2 COMPONENTS OF THE B-LYMPHOCYTE ANTIGEN RECEPTOR

The engagement of the B cell antigen receptor is the first step of ant igenic stimulation of B lymphocytes. This step is followed by a series of biochemical events, including the activation of protein-tyrosine k inases, phosphoinositide turnover, and multiple patterns of calcium mo bilization, which lead to the regulation of gene transcription and cel lular responses. The B cell antigen receptor complex is composed of me mbrane immunoglobulins (as antigen recognition subunits) and associate d chains (Ig-alpha and Ig-beta) that couple the receptor to cytoplasmi c protein kinases. To investigate independently the relative signaling capacity of Ig-alpha and Ig-beta, chimeric proteins containing their cytoplasmic domains were expressed in a B cell line. We found that Ig- alpha and Ig-beta activate two distinct intracellular signaling pathwa ys. The engagement of Ig-alpha chimeras induces a complete release of calcium from intracellular stores, followed by transmembrane calcium i nflux and late cell activation signals, detected by lymphokine secreti on. In contrast, Ig-beta chimeras do not induce lymphokine secretion o r calcium influx, but induce short oscillatory release of calcium, dep endent on the activity of the Ca-ATPase pump of the endoplasmic reticu lum. These results provide a structural basis for the diversity of B c ell responses.