A second amplifier function for the allergy-associated Fc epsilon RI-beta subunit

Genetics studies have identified the gene for the high-affinity IgE recepto r (Fc epsilon RI) beta subunit as a candidate gene for atopy. We have shown that beta is an intrinsic signaling amplifier leading to enhanced allergic responses in vivo. Here we report that beta has a second amplification fun ction: the amplification of Fc epsilon RI cell surface expression. This fun ction is due to an early association of beta with alpha, resulting in impro ved trafficking and maturation of alpha and receptor complexes. These data provide a possible molecular explanation for the large difference in Fc eps ilon RI density between beta(-)cells such as monocytes, dendritic cells, an d beta(+) effector cells (mast cells, basophils). In beta(+) cells, the com bined signaling and expression amplification results in an estimated 12- to 30-fold amplification of downstream events.