title: Intracellular induction pathways for CD23 antigen and surface immunoglobulins in human tonsillar B cells: the roles of protein kinase C and tyrosine kinase-mediated signals.
abstract: The expression of CD23 on human tonsillar B cells is increased following treatment with interleukin 4 (IL-4) or 12-O-tetradecanoylphorbol 13-acetate (TPA), while that of surface immunoglobulins (sIgs) is increased by IL-4 but decreased by TPA. This suggests that the signaling by these effectors may result from distinct second messenger-generating systems. In this study, we attempted to elucidate the signal transduction pathways responsible for the expression of CD23 and sIgs by using different protein kinase C (PKC) and tyrosine kinase (TK) inhibitors. Our results showed that B cells expressed varying amounts of sIgs depending on different activators and inhibitors. Sphingosine, a PKC inhibitor, almost completely reversed the TPA-induced decrease in sIgM and sIgD expression. Other PKC inhibitors, e.g., H7 and staurosporine, had similar but less profound effects. In comparison, the up-regulation of CD23 by IL-4 and TPA was only partially blocked by these PKC inhibitors. TK inhibitors, such as herbimycin A and genistein, decreased both the IL-4- and TPA-induced CD23 expression by 50-80%, but had modest effects on sIgs expression. These findings indicate that CD23 and sIgs expression is regulated by independent pathways; PKC is important for the regulation of sIgs expression while the signals through TK pathways might play the major role in CD23 expression.
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Cho
authors.forename: O
authors.initials: O
authors.lastname: Hwang
authors.forename: H B
authors.initials: HB
authors.lastname: Moon
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D016227:Benzoquinones; D006801:Humans; D007072:Immunoglobulin D / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D014066:Palatine Tonsil / Q000276:immunology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis*; D017455:Receptors, IgE / Q000096:biosynthesis*; D017828:Rifabutin / Q000031:analogs & derivatives; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D016227:Benzoquinones; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D047029:Lactams, Macrocyclic; D011809:Quinones; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE; D017828:Rifabutin; D015847:Interleukin-4; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate