Induction of kappa light chain synthesis in 70Z/3 B lymphoma cells by chemically defined lipid A precursors.
The murine B cell lymphoma 70Z/3 is a tumor line that resembles an early B cell. It responds to lipopolysaccharide by synthesizing kappa light chains, resulting in the appearance of surface IgM. We now demonstrate that this effect is triggered by the lipid A domain of lipopolysaccharide since a defined tetraacyl disaccharide 1,4'-bisphosphate precursor of mature lipid A, designated lipid IVA (Raetz, C. R. H., Purcell, S., Meyer, M. V., Qureshi, N., and Takayama, K. (1985) J. Biol. Chem. 260, 16080-16088), is fully active in stimulating kappa chain mRNA synthesis. In contrast, the monosaccharide lipid A precursor, lipid X, shows only slight activity; but a large excess of lipid X appears to complete with lipid IVA, partially blocking its effects. Mutants of the 70Z/3 line that are unresponsive to lipopolysaccharide also fail to respond to lipid IVA. The somatic cell system described here, coupled with the use of chemically defined agonists and antagonists, offers a new approach to understanding the early events in lipopolysaccharide/animal cell interactions.
D000818:Animals; D001402:B-Lymphocytes; D004926:Escherichia coli; D006017:Glycolipids / Q000494:pharmacology*; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis* / Q000235:genetics; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008223:Lymphoma / Q000276:immunology*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D012486:Salmonella typhimurium; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D006017:Glycolipids; D007145:Immunoglobulin kappa-Chains; D008050:Lipid A; D012333:RNA, Messenger; C040142:lipid A precursors, bacterial; C044283:lipid X