ALLERGY-ASSOCIATED FCR-BETA IS A MOLECULAR AMPLIFIER OF IGE-MEDIATED AND LGG-MEDIATED IN-VIVO RESPONSES

A role for the Fc receptor beta chain (FcR beta) in the pathogenesis o f 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 mechan istic explanation for its association with the development of atopy un clear. To address this controversy, we have generated novel mouse mode ls relevant to human Fc receptor function. Analysis of Fc epsilon RI- and Fc gamma RIII-dependent responses in these mice provides unequivoc al genetic evidence that FcR beta functions as an amplifier of early a nd late mast cell responses and, remarkably, in vivo anaphylactic resp onses.