Role of epitope density in the induction of tolerance and immunity with thymus-independent antigens. III. Interaction of epitope density and receptor avidity.

The induction of B cell tolerance to 2,4-dinitrophenyl conjugates of polysaccharide antigens (levan or dextran) was studied in mice primed with keyhole limpet hemocyanin (KLH) or 2,4,6-trinitrophenylated KLH. The relationship of the epitope density of the tolerogen with avidity of B cell receptors (as judged indirectly by a plaque inhibition assay) was investigated. It was found that high avidity precursors (IgG) were tolerized by antigen of much lower epitope density, and at lower concentration, than were low avidity precursors (especially IgM cells). IgA cells were intermediate in behavior. These results suggest that the epitope density effect acts by ensuring a necessary degree and/or energy of antigen binding.