SIGNALING EVENTS DURING HELPER T-CELL-DEPENDENT B-CELL ACTIVATION .1.ANALYSIS OF THE SIGNAL-TRANSDUCTION PATHWAYS TRIGGERED BY ACTIVATED HELPER T-CELL IN RESTING B-CELLS

gp39 is expressed on anti-CD3-activated Th, and binds CD40 on the B ce ll, driving B cell cycle entry. In this study, the signal-transduction pathway initiated in B cells as a consequence of interacting with act ivated Th is examined. Unlike anti-membrane Ig (anti-mig) or anti-MHC class II, plasma membranes (PM) isolated from anti-CD3-activated Th, P M(Act) did not trigger an increase in the B cell intracellular concent rations of cAMP or calcium. In addition, PM(Act) did not stimulate pro tein kinase C activation as measured by myristoylated alanine-rich C-k inase substrate (MARCKS) phosphorylation and protein kinase C transloc ation. The failure to detect these biochemical events may be caused by the asynchrony with which PM(Act) induce these normally transient bio chemical changes. Alternatively, PM(Act) may not trigger these events. PM(Act) did induce the tyrosine phosphorylation of several B cell sub strates. Neutralizing Abs directed against gp39 inhibited PM(Act)-indu ced protein tyrosine phosphorylation of B cell substrates. These resul ts suggest that cognate interactions in B cells initiate a signal-tran sduction pathway that is different from the pathway initiated by cross -linking of mlg or MHC class II.