Multiple signaling pathways mediate anti-Ig and IL-4-induced early response gene expression in human tonsillar B cells.
We have analyzed the relationship between the signaling pathways coupled to surface immunoglobulin and interleukin (IL)-4 receptors in human B cells from the patterns of expression of a panel of phorbol ester-inducible early response genes (ERG) activated by anti-IgM and IL-4 stimulation in vitro. Anti-IgM stimulation led to the induction of all eleven ERG tested. Two of these, the proto-oncogene, c-fos and an anonymous ERG 1R20 were insensitive to protein kinase C (PKC) inhibition with the drug, staurosporine and retained inducibility after down-regulation of PKC activity by purging with phorbol ester. These observations are consistent with previous data showing anti-IgM signaling through both PKC-dependent and PKC-independent pathways. c-fos and 1R20 were also the only ERG inducible in response to IL-4 stimulation and whilst ionomycin induced only c-fos, dibutyryl cyclic adenosine monophosphate stimulation led to induction of both c-fos and 1R20. These observations lend support to a role for the adenylate cyclase pathway being important for coupling of IL-4-generated signals to B cells responses. None of the anti-IgM-responsive ERG was further induced when B cells were co-stimulated with a combination of anti-IgM and IL-4, suggesting that the signaling cascades from these two agents are integrated downstream of third messenger pathways to synergistically promote B cell proliferation.
Murphy
J J
JJ
Division of Life Sciences, King's College London, GB.
Norton
J D
JD
D000470:Alkaloids / Q000494:pharmacology; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D005802:Genes, MHC Class II; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000235:genetics*; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D000090063:Proto-Oncogene Mas; D012313:RNA / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D019311:Staurosporine
D000470:Alkaloids; D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D015847:Interleukin-4; D012313:RNA; D011493:Protein Kinase C; D019311:Staurosporine