Functional consequences of FcɛRIα up‐regulation by IgE in human basophils

These studies examine the functional changes that occur after up‐regulation of FcɛRIα by immunoglobulin E (IgE) for human basophils. Basophils were cultured with and without IgE antibody (PS myeloma IgE or anti‐gp120‐specific IgE) for 1 week and challenged with anti‐IgE, anti‐FcɛRIα, or antigen for histamine and IL‐4 secretion. There were no statistically significant changes in their response to anti‐IgE or anti‐receptor antibodies, as compared with controls incubated for the same period, whereas receptor expression increased an average of 4‐fold. There was increased responsiveness to antigenic challenge, most notably at suboptimal concentrations of antigen (gp120 peptide‐ovalbumin conjugate). For a 6‐fold difference in cell surface density of gp120‐specific IgE, there was a 2.2‐fold change in antigen potency or 3‐fold increases in histamine release at lower antigen concentrations. Similar results were found for secretion of IL‐4. Basophil sensitivity, which is a measure of the density of antigen‐specific IgE required for 50% of maximal secretion, was used to determine whether up‐regulation of FcɛRIα was coordinated with up‐regulation of other components of the IgE‐signaling pathway. The results indicated up‐regulation of FcɛRI is not always accompanied by changes that allow sensitivity to be maintained. These results indicate that functional up‐regulation does occur but that its magnitude may be modulated because not all components of the signaling pathway are up‐regulated in a balanced manner.