Antibody-induced changes in levels of cyclic adenosine monophosphate in leukaemic lymphocytes

Abstract

When L2C leukaemic B lymphocytes from guinea-pigs were incubated in vitro with antibody directed to their surface immunoglobulin (Ig), a rapid rise in intracellular adenosine 3':5'-phosphate (cyclic adenosine monophosphate, cAMP) was observed. Estimation of cAMP was by a protein-binding assay using bovine adrenal protein kinase. Increases up to 30-fold occurred within 30 seconds of incubation at 37 degrees C, to be succeeded by a fall which reached the basal level between 5 and 7 min. The response was proportional to the amount of antibody present. Cross-linking of surface Ig by the antibody was necessary, bivalent (Fab'gamma)2 from the antibody gave a rise in cAMP similar to that given by the parent molecule, whereas monomeric Fab'gamma was ineffective unless it was subsequently cross-linked by anti-antibody. The rise was too rapid to have required capping of the surface Ig for its induction. Not all perturbations of the plasma membrane by antibody induce such a surge in cAMP, since anti-beta2 microglobulin, also reacting with the lymphocyte surface, failed to alter cAMP concentration. The results emphasize that immunotherapy can be influenced by antibody altering the metabolic activity of target cells, quite apart from activation of immunological cytotoxic pathways.