Evidence for a differential expression of the FcεRIγ chain in dendritic cells of atopic and nonatopic donors
Natalija Novak, … , Thomas Bieber, Stefan Kraft
Natalija Novak, … , Thomas Bieber, Stefan Kraft
Published April 1, 2003
Citation Information: J Clin Invest. 2003;111(7):1047-1056. https://doi.org/10.1172/JCI15932.
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Article Genetics

Evidence for a differential expression of the FcεRIγ chain in dendritic cells of atopic and nonatopic donors

Abstract

While mast cells and basophils constitutively express the high-affinity IgE receptor (FcεRI), it is absent or weakly expressed on APCs from normal donors. FcεRI is strongly upregulated on APCs from atopic donors and involved in the pathophysiology of atopic diseases. Despite its clinical relevance, data about FcεRI regulation on APCs are scarce. We show that in all donors intracellular α chain of the FcεRI (FcεRIα) accumulates during DC differentiation from monocytes. However, expression of γ chains of the FcεRI (FcεRIγ), mandatory for surface expression, is downregulated. It is low or negative in DCs from normal donors lacking surface FcεRI (FcεRIneg DCs). In contrast, DCs from atopics express surface FcεRI (FcεRIpos DCs) and show significant FcεRIγ expression, which can be coprecipitated with FcεRIα. In FcεRIneg DCs lacking FcεRIγ, immature and core glycosylated FcεRIα accumulates in the endoplasmic reticulum. In FcεRIpos DCs expressing FcεRIγ, an additional mature form of FcεRIα exhibiting complex glycosylation colocalizes with FcεRIγ in the Golgi compartment. IgE binding sustains surface-expressed FcεRI on DCs from atopic donors dependent on baseline protein synthesis and transport and enhances their IgE-dependent APC function. We propose that enhanced FcεRI on DCs from atopic donors is driven by enhanced expression of otherwise limiting amounts of FcεRIγ and is preserved by increased IgE levels.

Authors

Natalija Novak, Carmen Tepel, Susanne Koch, Klaudia Brix, Thomas Bieber, Stefan Kraft

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Figure 5

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Significant FcεRIγ expression and association of FcεRIα with FcεRIγ can ...
Significant FcεRIγ expression and association of FcεRIα with FcεRIγ can be detected only in FcεRIpos DCs from atopic donors. (a) FcεRIγ expression was determined by double immunolabeling of MoDCs using anti-FcεRIγ and anti-CD1a after a mild permeabilization with digitonin to preserve surface-expressed FcεRI complexes. Determination of FcεRI surface expression and flow-cytometric analysis was done as described for Figure 1. (b) FcεRIneg (4% positive cells) and FcεRIpos (86% positive cells) DCs were subject to mild lysis with a buffer containing 1% digitonin followed by immunoprecipitation using 3G6 anti-FcεRIα Ab and SDS-PAGE. FcεRIγ coprecipitated with FcεRIα was detected by immunoblotting using 4D8 Ab. PBMC lysates were used as positive controls.