title: Distinct Expression and Function of FcεRII in Human B Cells and Monocytes.
abstract: FcεRII is a multifunctional low-affinity IgER that is involved in the pathogenesis of allergic, inflammatory, and neoplastic diseases. Although discrepancies in FcεRII-mediated functions are being increasingly recognized, the consequences of FcεRII activation are not completely understood. In this study, we evaluated the expression of FcεRII on human blood cells and found that it was primarily expressed on monocytes and B cells. Although IL-4 promoted expression of the FcεRIIb isoform on B cells and monocytes, the expression of the FcεRIIa isoform was not dependent on IL-4. Furthermore, FcεRII predominantly bound allergen-IgE complexes on B cells but not on monocytes. FcεRII-mediated allergen-IgE complex uptake by B cells directed Ags to MHC class II-rich compartments. FcεRII-bearing monocytes and B cells expressed high levels of the FcεRII sheddase a disintegrin and metalloproteinase 10, which implies that they are important sources of soluble FcεRII. Moreover, we identified that IgE immune complex stimulation of FcεRII activated intracellular tyrosine phosphorylation via Syk in B cells but not in monocytes. Importantly, FcεRII-mediated signaling by allergen-IgE immune complexes increased IFN-γ production in B cells of allergic patients during the build-up phase of allergen-specific immunotherapy. Together, our results demonstrate that FcεRII mediates cell type-dependent function in allergic reactions. In addition, the results identify a novel allergen-IgE complex/FcεRII/Syk/IFN-γ pathway in allergic responses and suggest that FcεRII may play a role in regulating allergic reactions via modulating IFN-γ production in B cells.
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, 53127 Bonn, Germany; Wenming.Peng@ukb.uni-bonn.de.
authors.forename: Wenming
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, 53127 Bonn, Germany.
authors.forename: William
authors.initials: W
authors.lastname: Grobe
authors.affiliation: Institute of Clinical Chemistry and Pharmacology, University of Bonn, 53127 Bonn, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Walgenbach-Brünagel
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Flicker
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, 53127 Bonn, Germany.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Yu
authors.affiliation: Institute of Biochemistry and Molecular Biology, University of Bonn, 53127 Bonn, Germany.
authors.forename: Marc
authors.identifier: 0000-0002-4275-0200
authors.initials: M
authors.lastname: Sylvester
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, 53127 Bonn, Germany.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Allam
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, 53127 Bonn, Germany; and.
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Institute of Experimental Immunology, University of Bonn, 53127 Bonn, Germany.
authors.forename: Natalio
authors.initials: N
authors.lastname: Garbi
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, 53127 Bonn, Germany.
authors.forename: Natalija
authors.initials: N
authors.lastname: Novak
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D006967:Hypersensitivity; D015151:Immunoblotting; D047468:Immunoprecipitation; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D016133:Polymerase Chain Reaction; D017455:Receptors, IgE / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D017455:Receptors, IgE