ACTIVATION AND PROLIFERATION SIGNALS IN MOUSE B-CELLS .9. PROTEIN-KINASE C ACTIVATORS SYNERGIZE WITH NON-MITOGENIC ANTI-IMMUNOGLOBULIN ANTIBODIES TO DRIVE B-CELLS INTO G1

Intact (IgG) rabbit anti-Ig antibodies, unlike F(ab')2 fragments, do not induce DNA synthesis in murine B cells. The F(ab')2 antibodies induce prolonged breakdown of phosphatidylinositol bisphosphate, and hence activation of protein kinase C (PKC) in B cells, whilst the non-mitogenic antibodies stimulate an abortive response. In order to investigate the role of PKC in B-cell activation, the cells were cultured with combinations of F(ab')2 or intact anti-Ig together with the PKC-activating phorbol esters PDB or PMA. Both these agents synergized with intact anti-Ig to drive resting B cells into the G1 phase of the cell cycle. This is in line with the concept that intact anti-Ig does not induce substantial cell cycle progression in B cells because it fails to cause sufficient activation of PKC. The Ca2+ signal generated by this ligand is apparently sufficient to synergize with PKC activation by phorbol esters to induce B cells to progress into G1. However, the combination of phorbol esters with either form of anti-Ig failed to stimulate B cells to synthesize DNA. This probably reflects the capacity of these agents to inhibit DNA synthesis stimulated by F(ab')2 anti-Ig.