Activation and proliferation signals in mouse B cells. IX. 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.
Bijsterbosch
M K
MK
National Institute for Medical Research, Mill Hill, London, U.K.
McLaughlin
J B
JB
Holman
M
M
Klaus
G G
GG
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003524:Cyclosporins / Q000494:pharmacology; D004789:Enzyme Activation; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007399:Interphase; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D003524:Cyclosporins; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D010703:Phorbol Esters; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium