ACTIVATION OF LYN, BLK, AND BTK BUT NOT SYK IN CD72-STIMULATED B-LYMPHOCYTES

CD72 is a B cell-specific glycoprotein that has been shown to be impor tant for activation of mature B cells. Previously we showed that some of the early signaling events, such as calcium mobilization and phosph olipase-gamma activation, were similar in B cell Ag receptor (BCR)- an d CD72-stimulated B cells and that BCR- but not CD72-mediated early si gnaling events were blocked by protein kinase A activation, The presen t report shows that CD72 ligation induces a variety of tyrosine-phosph orylated proteins, most of which were of the same molecular mass as th ose seen in anti-IgM-treated B cells, except for a 72-kDa protein, Fur ther analysis showed that the tyrosine kinases lyn and blk were activa ted in CD72-ligated B cells, Interestingly, the non-src kinase syk was not activated in CD72-stimulated cells whereas the tec family kinase btk was activated in both CD72- and BCR-stimulated B cells, Furthermor e, B cells from rid mice were unresponsive to CD72-induced proliferati on, indicating an essential role for btk in CD72-induced signaling eve nts, Surprisingly, tyrosine phosphorylation of phospholipase C-gamma 2 was normal in CD72-stimulated cells in spite of a lack of activation of syk, Furthermore, B cell proliferation through CD72 was blocked by the immunosuppressive agents cyclosporin A and FK506, indicating the i mportant role for Ca2+-regulated activation events similar to BCR-stim ulated cells, We propose that btk can substitute for syk in inducing p hospholipase C-gamma 2 tyrosine phosphorylation and initiating calcium mobilization in CD72-stimulated B lymphocytes.