Adenosine 3',5'-cyclic monophosphate modulates the mitogenic responses of murine B lymphocytes

Adenosine 3',5'-cyclic monophosphate (cAMP) acts to inhibit a number of lymphocyte activities. The extent of this inhibition was tested by evaluating the effects of two cAMP-raising agents on B cell S phase entry induced by several different mitogenic regimens. It was found that both dibutyryl cAMP (dbcAMP) and isobutylmethylxanthine (IBMX) enhanced S phase entry induced by some regimens but inhibited S phase entry induced by others. The observed enhancing activity stands in contrast to the general notion of cAMP as being a "negative regulator," and it confirms that the observed inhibiting activity does not simply reflect cytotoxicity. Mitogenic regimens that appear to mimic each other, such as F(ab')2 fragments of goat anti-mouse immunoglobulin and the combination of a calcium ionophore and a phorbol ester, were distinguished by their responses to the addition of the two cAMP-raising agents. B cell responses were enhanced or inhibited even when dbcAMP was added 18-24 hr after the establishment of cultures. Cyclic AMP may regulate in a complex fashion S phase entry in cells of the immune system.