Role of receptor aggregation in triggering IgE-mediated reactions.

The first event in the IgE-mediated triggering of basophils and mast cells is the binding of serum IgE to membrane IgE receptors; quantitative relationships have been found among the serum IgE concentration, the number of IgE molecules per cell, the total receptor number, and the degree of endogenous receptor occupancy. Once bound, these antibody molecules must be cross-linked by multivalent antigen to activate the cell. Receptor juxtaposition is necessary throughout both activation and desensitization of these cells. Two types of desensitization occur. Antigen-specific desensitization alters only the function of certain IgE molecules; the cell can respond normally to other antigens. Specific desensitization is not reversed by removal of the antigen. Also, the affected antibody-receptor complexes remain on the cell surface, can rebind antigen, but cannot trigger the cell. Nonspecific desensitization is less well understood but is directly related to the number of cross-links on the basophils. Inasmuch as the cells become insensitive to all IgE-mediated stimuli, the total depletion of some intermediate has been postulated. In the presence of calcium the stimulated cells normally degranulate and release mediators. We have shown that for the simple antigens, both the release process and desensitization are a function of the number of cross-links present on the cell surface, and we have generated a mathematical model that quantitatively fits the experimental data. Thus, after many studies that span decades, the role of receptor aggregation in triggering mast cells and basophils is becoming qualitatively and quantitatively defined.