Competing Functions Encoded in the Allergy-Associated FcϵRIβ Gene

Allergic reactions are triggered via crosslinking of the high-affinity receptor for immunoglobulin E, FcϵRI. In humans, FcϵRI is expressed as a tetramer (αβγ2) and a trimer (αγ2). The β subunit is an amplifier of FcϵRI surface expression and signaling. Here, we show that as a consequence of alternative splicing, the FcϵRIβ gene encodes two proteins with opposing and competing functions. One isoform is the full-length classical β, the other a novel truncated form, βT. In contrast to β, βT prevents FcϵRI surface expression by inhibiting α chain maturation. Moreover, βT competes with β to control FcϵRI surface expression in vitro. We propose that the relative abundance of the products of the β gene may control the level of FcϵRI surface expression and thereby influence susceptibility to allergic diseases.