Activation of dense human tonsilar B cells. Induction of c-myc gene expression via two distinct signal transduction pathways.
Antibodies to surface Ig or to the B cell marker CD20 trigger resting human B cells in similar yet distinct ways. Either antibody induces five-fold increases in the expression of the protooncogene, c-myc, as detected with semi-quantitative Northern blot assays. The induction of c-myc mRNA by anti-IgM or anti-CD20 is blocked by inhibitors of protein kinase C (PKC) such as staurosporine and by pretreatment of B cells with phorbol esters to reduce cellular PKC levels. This suggests that PKC is involved in the pathways stimulated by both anti-IgM and anti-CD20. However, anti-CD20, unlike anti-IgM, does not activate significant increases in inositol triphosphate or intracellular-free calcium. Further, anti-CD20-triggered elevation of c-myc mRNA is inhibited by pertussis and cholera toxins, whereas the pathway initiated by anti-IgM if anything is stimulated by pertussis toxin and unchanged by cholera toxin. Further differences in the nature of these two signals were seen when the expression of adhesion/recognition molecules were examined. Anti-IgM consistently induces increased expression of the adhesion molecules CD54 (I-CAM-1) and B7/BB-1 on B cells, but anti-CD20 does not. Yet both anti-CD20 and anti-IgM increase class II MHC, CD18 (LFA-1 beta-chain) and LFA-3 levels. These data suggest that the way in which B cells are activated may influence their surface phenotype and possibly subsequent migration or cell-cell interactions.
Department of Biochemistry, University of Washington, Seattle 98195.
M W
MW
White
F
F
McConnell
G L
GL
Shu
D R
DR
Morris
E A
EA
Clark
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D002772:Cholera Toxin / Q000494:pharmacology; D015870:Gene Expression; D016259:Genes, myc; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D007295:Inositol Phosphates / Q000378:metabolism; D008213:Lymphocyte Activation; D014066:Palatine Tonsil / Q000276:immunology; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000502:physiology; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; D015815:Cell Adhesion Molecules; D007075:Immunoglobulin M; D007295:Inositol Phosphates; D010566:Virulence Factors, Bordetella; D002772:Cholera Toxin; D037342:Pertussis Toxin; D011493:Protein Kinase C