Membrane IgE Binds and Activates FcεRI in an Antigen-Independent Manner

Interaction of secretory IgE with FceRI is the prerequisite for allergen-driven cellular responses, fundamental events in immediate and chronic allergic manifestations. Previous studies reported the binding of soluble FceRIα to membrane IgE exposed on B cells. In this study, the functional interaction between human membrane IgE and human FceRI is presented. Four different IgE versions were expressed in mouse B cell lines, namely: a truncation at the Ce2-Ce3 junction of membrane IgE isoform long, membrane IgE isoform long (without Igα/Igβ BCR accessory proteins), and both eBCRs (containing membrane IgE isoforms short and long). All membrane IgE versions activated a rat basophilic leukemia cell line transfected with human FceRI, as detected by measuring the release of both preformed and newly synthesized mediators. The interaction led also to Ca2+ responses in the basophil cell line, while membrane IgE-FceRI complexes were detected by immunoprecipitation. FceRI activation by membrane IgE occurs in an Ag-independent manner. Noteworthily, human peripheral blood basophils and monocytes also were activated upon contact with cells bearing membrane IgE. In humans, the presence of FceRI in several cellular entities suggests a possible membrane IgE-FceRI-driven cell-cell dialogue, with likely implications for IgE homeostasis in physiology and pathology.