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

作者：Borkowski TA; Jouvin MH; Lin SY; Kinet JP^*

来源：The Journal of Immunology, 2001, 167(3): 1290-1296.

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 of allergic patients with anti-IgE Abs has been shown to induce a decrease in Fc epsilon RI expression on basophils and a decrease in Ag-triggered histamine release. However, the mechanisms underlying IgE-mediated regulation of Fc epsilon RI expression remain unclear. Here, we designed an in vitro model system to establish the minimal cellular requirements for regulation of Fc epsilon RI by IgE. Using this system, we demonstrate that transcriptional 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 level of expression. The mechanism of this up-regulation is the result of a combination of three factors: 1) stabilization of the receptor at the cell surface, which prevents receptor internalization and degradation; 2) use of a preformed pool of receptor comprising recycled and recently synthesized receptors; and 3) continued basal level of protein synthesis. It is possible that in vivo additional factors contribute to modulate the basic regulatory mechanism described here.

• 出版日期2001-8-1