Modulation of the B cell response to T-independent antigens by prostaglandins: evidence for effector system cross-talk.
The extracellular environment is a major factor in determining the responsiveness of a cell to particular stimuli. For example, E series prostaglandins suppress B cell responses to T-independent antigens, mitogen stimulation of DNA synthesis and proliferation, and the primary immune response. We investigated the effects of prostaglandins on the intracellular signals generated by receptor-coupled effector systems in B lymphocytes. Pretreating splenocytes from athymic nude mice with forskolin, PGE1, or PGE2 decreased the magnitude of anti-IgM-induced changes in cytosolic free [Ca2+]. Addition of 8-Br-cAMP, forskolin, PGE1, or PGE2 following stimulation with anti-IgM resulted in a decrease in the intracellular calcium signal measured by fluorescence-activated cell sorting using Indo-1 as a Ca2+ indicator. This decrease was not a result of an inhibition of influx across the plasma membrane. Thus activation of adenylate cyclase by prostaglandins modifies the generation of signals by phosphoinositidase C. This effector system cross-talk between adenylate cyclase and phosphoinositidase C is consistent with and may account for the inhibitory effects of prostaglandins in B cell responses.
Wiener
E
E
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Scarpa
A
A
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage; D000955:Antigens, T-Independent; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D007075:Immunoglobulin M; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology*
D000888:Antibodies, Anti-Idiotypic; D000955:Antigens, T-Independent; D007075:Immunoglobulin M; D011458:Prostaglandins E; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; C021491:glycerophosphoinositol glycerophosphodiesterase; D000262:Adenylyl Cyclases; D000527:Alprostadil; D015232:Dinoprostone; D002118:Calcium