SIGNALING THROUGH THE B-CELL ANTIGEN RECEPTOR REGULATES DISCRETE STEPS IN THE ANTIGEN-PROCESSING PATHWAY

Antigen processing in B cells is initiated by antigen binding to the s urface B cell antigen receptor (BCR), The ECR is a signaling receptor which also functions to endocytose bound antigen for subsequent intrac ellular processing and presentation with class II molecules. Previousl y, using subcellular fractionation, we showed that although the surfac e BCR constitutively traffics from the cell surface to the class II pe ptide-loading compartment (IIPLC), cross-linking the BCR regulates tra fficking, resulting in a more rapid movement of the BCR to the IIPLC ( Song ct at, 1995, J, Immunol, 155, 4255), The rate of degradation of b oth the BCR and the bound antigen was also accelerated following BCR c ross-linking. Here we provide evidence that the effect of crosslinking the BCR on antigen processing is in part dependent on signal cascades initiated by the BCR We show that the protein kinase inhibitors Genis tein and Chelerythrine, which block BCR signaling, reduce BCR-enhanced antigen processing in a dose dependent manner. The kinase inhibitors have a small effect on the rate of internalization of the BCR and anti gen following BCR cross-linking and significantly decrease the acceler ated trafficking to the IIPLC, The increased rate of degradation of th e BCR and antigen induced by BCR cross-linking is also decreased by th e kinase inhibitors. BCR signaling does not appear to have a global ef fect on intracellular membrane trafficking as cross linking the BCR di d not alter the rate of trafficking of newly synthesized class II mole cules to the IIPLC, Thus, the signaling function of the BCR appears to play a significant role in regulating discrete steps in the intracell ular antigen processing pathway, (C) 1998 Academic Press.