Allergy-associated FcRβ is a molecular amplifier of IgE- and lgG-mediated in vivo responses

A role for the Fc receptor beta chain (FcR beta) in the pathogenesis of allergy has been suggested by genetic studies. FcR beta is a subunit common to the high-affinity IgE (Fc epsilon RI) and low-affinity IgG (Fc gamma RIII) receptors, both of which contribute to the initiation of allergic reactions. Current in vitro data suggest that FcR beta can function as either a positive or negative regulator, leaving a mechanistic explanation for its association with the development of atopy unclear. To address this controversy, we have generated novel mouse models relevant to human Fc receptor function. Analysis of Fc epsilon RI- and Fc gamma RIII-dependent responses in these mice provides unequivocal genetic evidence that FcR beta functions as an amplifier of early and late mast cell responses and, remarkably, in vivo anaphylactic responses.