Functional consequences of Fc epsilon RI alpha up-regulation by IgE in human basophils

These studies examine the functional changes that occur after up-regulation of Fc epsilon RI alpha by immunoglobulin E (IgE) for human basophils, Baso phils were cultured with and without IgE antibody (PS myeloma IgE or anti-g p120-specific IgE) for 1 week and challenged with anti-IgE, anti-Fc epsilon RI alpha, or antigen for histamine and IL-4 secretion. There were no stati stically significant changes in their response to anti-IgE or anti-receptor antibodies, as compared with controls incubated for the same period, where as receptor expression increased an average of 4-fold. There was increased responsiveness to antigenic challenge, most notably at suboptimal concentra tions of antigen (gp120 peptide-ovalbumin conjugate), For a 6-fold differen ce in cell. surface density of gp120-specific IgE, there was a 2.2-fold cha nge in antigen potency or 3-fold increases in histamine release at lower an tigen concentrations. Similar results were found for secretion of IL-4. Bas ophil sensitivity, which is a measure of the density of antigen-specific Ig E required for 50% of maximal secretion, was used to determine whether up-r egulation of Fc epsilon RI alpha was coordinated with up-regulation of othe r components of the IgE-signaling pathway. The results indicated up-regulat ion of Fc epsilon RI is not always accompanied by changes that allow sensit ivity to be maintained. These results indicate that functional up-regulatio n does occur but that its magnitude may be modulated because not all compon ents of the signaling pathway are up-regulated in a balanced manner.