Protein kinase C activation in B cells by indolactam inhibits anti-Ig-mediated phosphatidylinositol bisphosphate hydrolysis but not B cell proliferation.
In order to examine the role of phosphatidylinositol bisphosphate (PIP2) hydrolysis in B cell activation, we studied the effect of various classes of protein kinase C (PKC) activators on anti-Ig-mediated B cell stimulation. Anti-Ig-stimulated PIP2 hydrolysis, elevations in [Ca2+]i, and induction of DNA synthesis were inhibited by PMA (a phorbol ester) as previously reported. In contrast, indolactam (an alkaloid PKC activator) inhibited PIP2 hydrolysis and elevations in [Ca2+]i, but stimulated rather than inhibited cellular proliferation. In order to examine whether the binding avidity of the PKC activators to PKC played a role in determining their activity to stimulate or inhibit B cell activation, we studied two other PKC activators, bryostatin and mezerein. Again, both inhibited anti-Ig mediated PIP2 hydrolysis and elevations in [Ca2+]i, whereas only the former inhibited induction of DNA synthesis. These data suggest that a) high levels of PIP2 hydrolysis and elevations in [Ca2+]i are not essential for anti-Ig-mediated induction of B cell DNA synthesis and b) activation of PKC may induce both stimulatory and inhibitory pathways of B cell activation, and whether stimulation or inhibition of cell activation is observed may depend on the combined intensity of these two signals.
Mond
J J
JJ
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Balapure
A
A
Feuerstein
N
N
June
C H
CH
Brunswick
M
M
Lindsberg
M L
ML
Witherspoon
K
K
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology*; D054713:Bryostatins; D002118:Calcium / Q000378:metabolism; D004224:Diterpenes; D004789:Enzyme Activation / Q000187:drug effects; D007138:Immunoglobulin delta-Chains / Q000276:immunology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D007769:Lactams / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D018942:Macrolides; D051379:Mice; D008811:Mice, Inbred DBA; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D054713:Bryostatins; D004224:Diterpenes; D007138:Immunoglobulin delta-Chains; D007211:Indoles; D007769:Lactams; D007783:Lactones; D018942:Macrolides; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D011947:Receptors, Antigen, B-Cell; D013729:Terpenes; C011309:mezerein; C046785:bryostatin 1; D015759:Ionomycin; C043969:indolactam V; D011493:Protein Kinase C; D002118:Calcium