IgE-regulated loss, not IgE-regulated synthesis, controls expression of Fcepsilon Rl in human basophils

Expression of the high-affinity receptor on basophils and mast cells is mod ulated by immunoglobulin E (IgE) antibody. Recent studies have shown that m odulation occurs through interaction of IgE with the receptor itself, but t he mechanisms underlying this control are not understood. Taking both a the oretical and experimental approach, we examined several competing models th at focus on whether there is IgE-regulated loss, IgE-regulated synthesis, o r both regulated loss and synthesis of the Fc receptor for IgE (Fc epsilon RI). We report that removing IgE from occupied Fe epsilon RI resulted in an accelerated loss only in the unoccupied receptor, with no loss of occupied receptors and no loss of total receptors when all receptors were occupied. Together with previous studies, these results establish that there was IgE -regulated loss of receptors. An examination of synthetic rates of Fc epsil on RI alpha using pulse-labeling with S-35-methionine indicated no differen ce in synthetic rates in the presence or absence of IgE. Similarly, the pre sence or absence of IgE had no influence on the levels of mRNA for either a lpha, beta, or gamma subunits of Fc epsilon RI. Using model simulations, we found that regulated-synthesis models could be distinguished from regulate d-loss/ constant-synthesis models on the basis of the relationship between starting Fc epsilon RI densities and changes in density after culture for I week in the absence of IgE. Experimental data from this type of study fit a regulated-loss model that did not include regulation of synthesis. Taken together, these results suggest that IgE regulates cell surface expression of Fc epsilon RI only by regulating the rate that receptor is lost from the cell surface.