Serum IgE clearance is facilitated by human FcεRI internalization
Alexandra M. Greer, Nan Wu, Amy L. Putnam, Prescott G. Woodruff, Paul Wolters, Jean-Pierre Kinet, Jeoung-Sook Shin
Alexandra M. Greer, Nan Wu, Amy L. Putnam, Prescott G. Woodruff, Paul Wolters, Jean-Pierre Kinet, Jeoung-Sook Shin
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Research Article Immunology

Serum IgE clearance is facilitated by human FcεRI internalization

Abstract

The high-affinity IgE receptor FcεRI is constitutively expressed in mast cells and basophils and is required for transmitting stimulatory signals upon engagement of IgE-bound allergens. FcεRI is also constitutively expressed in dendritic cells (DCs) and monocytes in humans; however, the specific functions of the FcεRI expressed by these cells are not completely understood. Here, we found that FcεRI expressed by human blood DC antigen 1–positive (BDCA1+) DCs and monocytes, but not basophils, traffics to endolysosomal compartments under steady-state conditions. Furthermore, IgE bound to FcεRI on BDCA1+ DCs was rapidly endocytosed, transported to the lysosomes, and degraded in vitro. IgE injected into mice expressing human FcεRIα (FCER1A-Tg mice) was endocytosed by conventional DCs and monocytes, and endocytosis was associated with rapid clearance of circulating IgE from these mice. Importantly, this rapid IgE clearance was dependent on monocytes or DCs but not basophils. These findings strongly suggest that constitutive internalization of human FcεRI by DCs and monocytes distinctively contributes to serum IgE clearance.

Authors

Alexandra M. Greer, Nan Wu, Amy L. Putnam, Prescott G. Woodruff, Paul Wolters, Jean-Pierre Kinet, Jeoung-Sook Shin

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Figure 2

FcεRI is localized in the lysosomes of DCs and monocytes.

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FcεRI is localized in the lysosomes of DCs and monocytes. (A–D) Intracel...
(A–D) Intracellular localization of hFcεRI in blood basophils (A), blood BDCA1+ DCs (B), lung BDCA1+ DCs (C), and blood monocytes (D). Each cell type was isolated as described in Methods, stained using the indicated antibodies, and examined by confocal microscopy. Basophil images are representative of at least 48 recorded images from at least 7 unique and representative donors. Blood DC images are representative of at least 25 recorded images from 2–6 unique and representative donors. The lung DC image is representative of 10 images from 4 unique and representative donors. The monocyte image is representative of 26 recorded images from 3 unique and representative donors. For all confocal images, original magnification is ×60, scale bars are 2.5 μm, and negligible staining by isotype control antibodies was confirmed (Supplemental Figure 2). (E) FcεRIα maturation state in basophils and DCs. FcεRIα was immunoprecipitated from blood basophil and blood BDCA1+ DC lysates. Half of the immunoprecipitates were treated with EndoH. The resulting samples were run on SDS-PAGE, transferred, and blotted with an FcεRIα antibody. The asterisk indicates EndoH that cross-reacted with FcεRIα antisera.