IMMUNONS REVISITED - BINDING OF MULTIVALENT ANTIGENS TO B-CELLS

The T-independent B cell response induced by highly multivalent hapten -polymer preparations has been studied extensively. The in vitro measu red dose-response curve lends to be roughly bell-shaped with the peak response occurring at very low ligand concentrations, between 0.1-1 ng /ml for a variety of different ligands. Furthermore. polymers with mor e than approximately 10 haptens tend to be stimulatory, whereas polyme rs with fewer than 10 haptens conjugated, tend to be inhibitory. These observations have been perplexing when viewed within the context of s tandard theories of receptor ligation by multivalent ligands. We prese nt a new analysis of these previous experiments that reconciles the di fferences between theory and experiment. From this theory it is conclu ded that the peak in the observed dose-response curve only weakly refl ects properties of the ligand and the affinity of surface immunoglobul in for the hapten, but depends strongly on the density of antigen-spec ific B cells in the culture. The number of responding cells decreases at low ligand concentrations, because cells have to share limiting amo unts of ligand and not because of the decreasing probability of recept ors and ligands meeting each other. Our theory leads to the same concl usion as made by previous researchers, namely that a minimum number of receptor sites, of the order of 10, need to be bound to a single liga nd in order to stimulate a B cell. While this conclusion was based on the lack of immunogenicity of antigens carrying less than a minimum nu mber of haptens, the quantitative results of this study, derived from fitting experimental dose-response curves obtained with highly multiva lent antigens, provide evidence for the immunon hypothesis that is bas ed upon the degree of receptor aggregation. Our theory also provides q uantitative agreement with experimental observations on systems, in wh ich both stimulatory and non-stimulatory polymers are mixed in the sam e system. (C) 1997 Elsevier Science Ltd.