Minimal requirements for IgE-mediated regulation of surface Fc epsilon RI

The IgE-Fc epsilon RI network plays a central role in allergic inflammation . IgE levels control cell surface levels of Fc epsilon RI and, in turn, Fc epsilon RI levels modulate the intensity of effector responses. Treatment o f allergic patients with anti-IgE Abs has been shown to induce a decrease i n Fc epsilon RI expression on basophils and a decrease in Ag-triggered hist amine release. However, the mechanisms underlying IgE-mediated regulation o f Fc epsilon RI expression remain unclear. Here, we designed an in vitro mo del system to establish the minimal cellular requirements for regulation of Fc epsilon RI by IgE. Using this system, we demonstrate that transcription al regulation, hemopoietic-specific factors, and signaling are not required for IgE-mediated increases in Fc epsilon RI expression. IgE binding to the alpha -chain is the minimal requirement for the induction of Fc epsilon RI up-regulation. The rate of up-regulation is independent of the baseline le vel of expression. The mechanism of this up-regulation is the result of a c ombination of three factors: 1) stabilization of the receptor at the cell s urface, which prevents receptor internalization and degradation; 2) use of a preformed pool of receptor comprising recycled and recently synthesized r eceptors; and 3) continued basal level of protein synthesis. It is possible that in vivo additional factors contribute to modulate the basic regulator y mechanism described here.