The role of I-A/E molecules in B-lymphocyte activation. II. Mechanism of inhibition of the responses to lipopolysaccharide by anti-I-A/E antibodies.
We have previously demonstrated that monoclonal anti-I-A/E antibodies inhibit B-cell responses to lipopolysaccharide (LPS). In the present report, the inhibitory effects were shown to be carried out directly on B cells, and to be totally independent of the LPS concentration used, thereby showing that antibodies do not mediate their effect through blocking of accessory cells or steric hindrance of LPS-receptors. Of the three different phases in B-cell activation/induction, proliferation, and maturation, induction was shown to be the most sensitive to inhibition by anti-I-A/E antibodies. Thus, kinetic studies showed that anti-I-A/E antibodies are only inhibitory for the first 16 h of LPS activation, after which B cells can no longer be inhibited by these antibodies. Class II MHC molecules appear, therefore, to be part of a membrane molecular complex which regulates delivery of activation signals to resting B cells. Since it was also shown that this time period corresponds approximately to the time required for B cells to express functional reactivity to growth factors, we suggest that anti-I-A/E antibodies act on resting B lymphocytes to inhibit mitogen-dependent induction of growth receptor expression.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001667:Binding, Competitive / Q000187:drug effects; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D008070:Lipopolysaccharides