THE COMPLEXITY OF SIGNALING PATHWAYS ACTIVATED BY THE BCR

Cross-linking of the B cell antigen receptor (BCR) leads to the activa tion of three types of intracellular protein tyrosine kinases. These t yrosine kinases then phosphorylate signaling components to activate a variety of signaling reactions, including phosphatidylinositol 4,5-bis phosphate hydrolysis, Ras activation, and phosphatidylinositol 9-kinas e activation. Each of these signaling reactions, and also the signalin g molecules Vav and HS1, appears to be important for at least some of the many types of B cell responses to antigen. The complexity of BCR s ignaling reactions may be required to allow the B cell to respond in a number of distinct ways to antigen (proliferation, survival, apoptosi s, maturational arrest, etc.) depending on the maturation state of the B cell, the location in the body, the physical nature of the antigen, and the possible presence of the antigen in complex with antibody or complement components.