The FcεRIβ Subunit Functions as an Amplifier of FcεRIγ-Mediated Cell Activation Signals

AbstractThe high affinity IgE receptor (FcεRI) plays a central role in the initiation of allergic responses. FcεRI is multimeric and is expressed as either αγ2 trimers or αβγ2 tetramers. Recently, polymorphisms of the β chain gene have been associated with the development of various allergic phenotypes. Until now, the role of β in FcεRI-dependent signaling was largely unknown. For that reason, we compared the signaling characteristics of various wild-type and mutant αγ2 and αβγ2 FcεRI complexes. These studies demonstrate that the γ dimer functions as an autonomous activation module, while β functions as an amplifier that provides a gain of 5- to 7-fold, as measured by Syk activation and calcium mobilization