Regulation of lipopolysaccharide-induced B-cell activation: evidence that surface immunoglobulin mediates two independently regulated signals.
An antigen-specific B cell response can be induced by low concentrations of haptenated lipopolysaccharide (LPS), whereas high concentrations are inhibitory. Two explanations have been proposed for the latter phenomenon. In the first, specific surface Ig focuses LPS to the B cell membrane, where high local concentrations of the mitogen become paralytic for B cell responses. In the alternative, transmission of an antigen signal at higher concentrations of hapten LPS actively inhibits the development of antibody secreting cells (ASC). In the present paper, the immunosuppressant cyclosporine A (CsA) was used to attempt to distinguish between these two models. Cyclosporine A did not block the inhibitory effects of goat anti-IgM (galphaIgM) on development of ASC induced by LPS and therefore was unsuitable for testing between the two models. However, surprisingly, in the presence but not the absence of CsA, even low concentrations of galphaIgM became inhibitory for LPS-induced B cell proliferation. Thus, a CsA-insensitive signal could inhibit both B cell proliferation and the development of ASC. In contrast, the CsA-sensitive signal induced by sIg required high concentrations of galphaIgM for triggering and enhanced the LPS proliferative response without affecting development of ASC. Evidence is presented that these two signals are regulated independently, suggesting that together they may transmit information about the physical form of an antigen to the B cell.
Mamchak
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Medical Foundation of the University of Sydney, Centenary Institute of Cancer Medicine and Cell Biology, Sydney, New South Wales.
Hodgkin
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PD
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D007075:Immunoglobulin M / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008808:Mice, Inbred CBA; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013997:Time Factors
D000906:Antibodies; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; D016572:Cyclosporine