New Insights on the Allergy-Linked β Subunit of the High Affinity IgE Receptor: Mechanisms and Clinical Implications

The high affinity IgE Fc receptor (FcεRI) on mast cells and basophils has a central role in allergy and asthma. The β subunit of this multimeric receptor is a membrane tetra-spanning protein that encodes a nonconventional immunoreceptor tyrosine-based activation motif (ITAM) that imparts it signaling competence. This subunit was shown to amplify FcεRI signaling causing increased cellular responses such as degranulation. Polymorphisms of the β subunit have been linked to atopy, asthma, and allergy. Although considerable effort has been made to understand the functional consequence(s) of expressing these polymorphisms, the outcome has not been revealing. Recent studies show a link between β subunit polymorphisms, β gene transcription, and increased FcεRI expression. Additionally, a newly described function for the β subunit suggests an important role in downregulating cytokine production. Among the molecules whose response is dampened by FcεRIb is NFkB, a central regulator of inflammation. Collectively, these studies suggest that the β subunit is important in controlling the sensitivity and extent of an elicited response upon mast cell or basophil activation. Thus the findings, described herein, provide new insights on the mechanistic link between the FcεRIb and allergic disease.