title: Absence of lipopolysaccharide high-dose paralysis in B-cell responses: implications for the one-signal theory.
abstract: Over 20 years ago, Coutinho and Möller reported that high concentrations of LPS were paralytic for the development of antibody secreting cells (ASC). This data was used to explain bell-shaped dose-response curves observed for antihapten antibody formation in response to haptenated LPS. In turn, this bell curve was used to formulate the one-signal model of B cell activation, which argued that antigen signalling was generally unimportant to B cell responses. The present paper re-examines LPS dose-response curves and finds results that do not support the view that high doses of LPS inhibit B cell differentiation to ASC. If high-dose paralysis is not an attribute of LPS stimulation, then the bell-shaped dose curve for hapten-specific ASC originally observed by Coutinho and Möller required an alternative explanation. Through the use of haptenated Ficoll, it was possible to show that the generation of LPS-induced antitrinitrophenol ASC could be inhibited by antigen presented on an inert substrate. Thus, the transmission of surface Ig-mediated (antigen) signals at higher concentrations can explain the antihapten bell-shaped dose curves, in contradiction to the conclusions of the one-signal model.
authors.affiliation: Medical Foundation of the University of Sydney, Centenary Institute of Cancer Medicine and Cell Biology, Sydney, New South Wales.
authors.forename: A A
authors.initials: AA
authors.lastname: Mamchak
authors.forename: P D
authors.initials: PD
authors.lastname: Hodgkin
mesh_terms: D000818:Animals; D000906:Antibodies / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D014301:Trinitrobenzenes / Q000276:immunology / Q000494:pharmacology
chemical_list: D000906:Antibodies; D003470:Culture Media; D008070:Lipopolysaccharides; C020529:TNP-ficoll; D014301:Trinitrobenzenes; D005362:Ficoll