Minimal requirements for IgE-mediated regulation of surface Fc epsilon RI.
The IgE-FcepsilonRI network plays a central role in allergic inflammation. IgE levels control cell surface levels of FcepsilonRI and, in turn, FcepsilonRI levels modulate the intensity of effector responses. Treatment of allergic patients with anti-IgE Abs has been shown to induce a decrease in FcepsilonRI expression on basophils and a decrease in Ag-triggered histamine release. However, the mechanisms underlying IgE-mediated regulation of FcepsilonRI expression remain unclear. Here, we designed an in vitro model system to establish the minimal cellular requirements for regulation of FcepsilonRI by IgE. Using this system, we demonstrate that transcriptional regulation, hemopoietic-specific factors, and signaling are not required for IgE-mediated increases in FcepsilonRI expression. IgE binding to the alpha-chain is the minimal requirement for the induction of FcepsilonRI 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.
Borkowski
T A
TA
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Jouvin
M H
MH
Lin
S Y
SY
Kinet
J P
JP
D016475:3T3 Cells; D000818:Animals; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D005784:Gene Amplification / Q000276:immunology; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism / Q000502:physiology*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011498:Protein Precursors / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017455:Receptors, IgE / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D011498:Protein Precursors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE; D007073:Immunoglobulin E; D003513:Cycloheximide