The role of I-A/E molecules in B lymphocyte activation. I. Inhibition of lipopolysaccharide-induced responses by monoclonal antibodies.
A panel of 22 different monoclonal antibodies, including specificities against various antigenic clusters of I-A and I-E molecules, were probed over a wide range of concentrations for their ability to inhibit lipopolysaccharide-induced B lymphocyte proliferation and maturation to immunoglobulin-secreting plaque-forming cells (PFC). Most antibodies were competent to inhibit up to 80 to 100% of the response of appropriate target cells, although having little or no effect on irrelevant spleen cell cultures. Mixtures of either anti-I-A or anti-I-E specificities were more efficient inhibitors than individual antibodies, as shown by the average concentrations required for 50% inhibition (30 and 300 ng/ml, respectively). The selective role of I-A/E molecules in B cell activation was demonstrated by the failure of anti-K antibodies of the same isotype, bound in comparable amounts to target cells, to modulate B cell responses in parallel cultures. Fc receptor-mediated inhibitory effects were further excluded by equivalent inhibition obtained with anti-I-A antibodies of the IgM class. Anti-I-A/E antibodies appear to inhibit the inductive phase of B cell responses, as suggested by limiting dilution experiments performed in the presence of 50% inhibitory concentrations of antibodies: 50% of the control number of reactive clones were found to respond, but those that escaped inhibition developed to control sizes of progenies producing PFC.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000918:Antibody Specificity; D000921:Antibody-Producing Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D006462:Hemolytic Plaque Technique; D006649:Histocompatibility Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011961:Receptors, Fc / Q000502:physiology
D000911:Antibodies, Monoclonal; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D008070:Lipopolysaccharides; D011961:Receptors, Fc