The Journal of Immunology, Vol 144, Issue 2 451-455, Copyright © 1990 by American Association of Immunologists
Protein kinase C activation in B cells by indolactam inhibits anti-Ig- mediated phosphatidylinositol bisphosphate hydrolysis but not B cell proliferation
JJ Mond, A Balapure, N Feuerstein, CH June, M Brunswick, ML Lindsberg and K Witherspoon
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
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.
