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

Abstract

Summary.-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°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'y)2 from the antibody gave a rise in cAMP similar to that given by the parent molecule, whereas monomeric Fab'y 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-/2 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.

Preliminary experience in treating lymphocytic leukaemia with antibody to immunoglobulin idiotypes on the cell surfaces

“…A limited amount of evidence available from animal work supports this assumption (Kassell et al, 1973;Bernstein et at., 1980). Other pos-500 sible anti-tumour mechanisms operative through antibody include simple metabolic perturbation (Virji & Stevenson, 1979) complement-independent opsonization (Fakhri et al, 1973) and K-cell lysis (MacLennan, 1972). In sheep antibodies, K-cell lysis is promoted by the IgG2 subclass (Stevenson & Elliott, 1978) which was removed from our preparation because of its blocking activity for complement lysis.…”