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

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