Activation of B-lymphocytes during an adaptive immune response is dictated by the meticulous co- ordination of the strength and quality of signals transmitted via the B cell receptor (BCR) and various co-receptors. Our laboratory has extensively studied the functional importance of one such B cell specific co-receptor, CD72, during B cell activation. CD72 activates protein tyrosine kinase pathways resulting in syk-independent activation of phospholipase-C (PLC) γ2. and calcium mobilization. CD72 mediated B cell activation is dependent on the physical and functional interaction with another co-receptor, CD 19, which is a part of a multimeric complex with the complement receptor 2.  The association with CD 19 enables CD72 to activate phosphatidylinositol 3-kinase (PI 3-K). The outcome of CD72 activation is the proliferation of mature B cells and enhancement of BCR induced growth and differentiation responses. CD72 triggering fails to induce growth responses in immature B cells and peritoneal B-l cells. Unlike BCR signaling, CD72 activation is resistant to the inhibitory effects of inflammatory mediators such as prostaglandin E2 and interferon γ. This provides a means to sustain B cell activation during acute inflammatory reactions. Recent studies have shown that CD72 can also negatively influence BCR signaling by recruiting a src-homology 2 domain containing tyrosine phosphatase, SHP-1. CD72 deficient mice show a mild increase in BCR dependent calcium mobilization and B cell proliferation. Overall, these studies point to a novel dual regulatory function of CD72 in B cell activation.