Molecular events in B cell activation. I. Signals required to stimulate G0 to G1 transition of resting B lymphocytes.
Anti-immunoglobulin antibodies (anti-Ig) can stimulate a majority of resting B cells via their receptor Ig. Evidence suggests that the signals generated after this ligand-receptor interaction may be transduced via hydrolysis of inositol phospholipids. In other systems, the ability of inositol phospholipid hydrolysis to link receptor-ligand interactions to subsequent activational events has been suggested to relate to the ability of metabolic intermediates of this hydrolytic process to facilitate activation of protein kinase C and mobilization of Ca+2. In this study, we investigated the importance of protein kinase C and Ca+2 mobilization in the signaling mechanism by which anti-Ig drives B cells to undergo G0 to G1 transition. Our results show that pharmacologic inhibition of either protein kinase C activity or channel-mediated Ca+2 influx completely abrogates the increase in RNA synthesis associated with B cell activation after stimulation by anti-Ig. This suggests that pathways leading to both protein kinase C activation and elevation of intracellular Ca+2 are critical for receptor Ig-mediated G0 to G1 transition. Furthermore, studies in which anti-Ig-induced signaling could be bypassed by directly facilitating Ca+2 mobilization and protein kinase C activation using Ca+2 ionophore and phorbol diester show that these events are sufficient to drive the majority of resting B cells into G1 in the absence of additional signaling from accessory cells or extra-cellular factors. However, like anti-Ig-induced stimulation, Ca+2 ionophore and phorbol diester are relatively inefficient in driving B cells that have entered G1 into S phase. We discuss the relevance of these results towards the transduction mechanism linking B cell membrane-associated Ig-generated signals with subsequent activation events.
Monroe
J G
JG
Kass
M J
MJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D007399:Interphase / Q000187:drug effects; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D011493:Protein Kinase C; D011494:Protein Kinases / Q000502:physiology; D012313:RNA / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011947:Receptors, Antigen, B-Cell; D000001:Calcimycin; D012313:RNA; D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium