CD72-MEDIATED B-CELL ACTIVATION INVOLVES RECRUITMENT OF CD19 AND ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE

Occupancy of the B cell glycoprotein, CD72 results in syk-independent activation of phospholipase-C gamma and calcium mobilization. The cyto plasmic tail of CD72 does not contain an immunoreceptor tyrosine-based activation motif to directly transduce signals into the B lymphocyte. Hence, we investigated whether other coreceptors such as CD19 and its associated phosphatidylinositol 3-kinase (PI 3-K) were involved in CD 72 signaling. Two specific inhibitors of PI 3-K inhibited CD72-stimula ted B cell proliferation in a dose-dependent manner. Activation of B l ymphocytes via CD72 resulted in recruitment and activation of PI 3-K, which was mediated by CD19. Accordingly, CD72 ligation induced CD19 ty rosine phosphorylation. Thus, lipid products generated as a result of Pi 3-K activation may have an important function in CD72-mediated B ly mphocyte activation. The kinetics of CD19 tyrosine phosphorylation ind uced by CD72 ligation were strikingly different from those seen follow ing B cell antigen receptor (BCR) stimulation. A transient increase in the tyrosine phosphorylation of the complement receptors, CD21 and CD 35 was observed in BCR- but not CD72-stimulated cells. Go-cross-linkin g of CD72 and CD19 failed to induce syk tyrosine phosphorylation sugge sting that even under these conditions, CD72 signaling was independent of syk activation. A transient and stimulation-dependent physical ass ociation between CD19 and CD72 was observed in CD72-ligated cells. The se observations suggest a mechanism by which CD72 can recruit CD19 and influence activation of CD19-associated PI 3-K, which appears to be c ritical for CD72-mediated B cell activation.