Products from the hydrolysis of phosphatidylinositol 4,5-bisphosphate (IP3) can increase and/or potentiate cAMP accumulation in a variety of cells. Antibody to surface immunoglobulins activates IP3 hydrolysis in B-lymphocytes. In this study we have examined whether anti-Ig also stimulated and/or potentiated increases in the cAMP levels of splenocytes from athymic nude mice. Furthermore, since TPA potentiates anti-Ig-induced DNA synthesis and cAMP modulates DNA synthesis, the effects of TPA on any anti-Ig-induced changes in cAMP were also studied. Antibody (25 μg/ml) stimulated a rapid rise in cAMP which increased from 250 fmol/106 cells to 400 fmol/106 cells within 1 min and then subsided to 310 fmol/106 cells by 10 min. TPA (96 nM) suppressed the anti-Ig-induced cAMP accumulation at 1 min by 60%, but potentiated the forskolin (114 μM)-induced rise by 151%. Two other activators of protein kinase C, dioctanoylglycerol (5 μM), and anti-Ig (25 μg/ml), also potentiated the forskolin response by 198% and 52%, respectively. These results suggest that modulation of the adenylate cyclase system by anti-Ig may act in concert with cytokines and/or prostaglandins secreted by other lymphoid cells to define the state of proliferation or differentiation in B-cells.
