IgG-mediated down-regulation of IgE bound to mast cells: a potential novel mechanism of allergen-specific desensitization

Allergy
Christina UermösiMartin F Bachmann

Abstract

Allergen-specific IgGs are known to inhibit IgE-mediated mast cell degranulation by two mechanisms, allergen-neutralization and engagement of the inhibitory FcγRIIB recruiting the phosphatase SHIP-1. Here we unravel an additional mechanism of IgG-mediated mast cell desensitization in mice: down-regulation of allergen-specific IgE. Mast cells were loaded in vitro and in vivo with monoclonal IgE antibodies specific for Fel d1 and exposed to immune complexes consisting of Fel d1-specific IgG antibodies recognizing different epitopes. Down regulation of IgE was followed by flow cytometry. Mast cells loaded with 2 different IgE antibodies efficiently internalized the IgE antibodies if exposed to recombinant Feld d1. In contrast, no down-regulation occurred if mast cells were loaded with IgE antibodies exhibiting a single specificity before stimulation with recombinant Fel d1 [corrected]. Interestingly, however, IgEs of a single specificity were rapidly down-regulated in vitro and in vivo in the presence of Fel d1-specific monoclonal IgGs recognizing another epitope on Fel d1. Despite FceRI-internalization, little calcium flux or mast cell degranulation occurred. FcγRIIB played a dual role in the process since it enhanced IgE interna...Continue Reading

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