IgE Signaling Selectively Suppresses FceRI Beta Chain Expression (139.2)

Abstract

Abstract Mast cells are critical players in allergic disease mediated by IgE and FcεRI interactions. In mice, FcεRI functions as a tetramer, composed of an IgE binding alpha subunit, two ITAM bearing gamma subunits, and a signal enhancing/amplifying beta subunit. Little is known about beta chain regulation. We activated mast cells with IgE + antigen and determined the resulting effects on beta chain mRNA, protein levels and surface expression. IgE crosslinkage inhibited beta chain mRNA expression, with a nadir at 5 hours post-stimulation. This was matched by reduced expression of the beta chain, with no change in the alpha or gamma subunits. A truncated form of beta, termed beta-t, may suppress IgE receptor expression. We found that IgE-mediated signaling also inhibited beta-t expression, and that beta-t was slower to return to baseline levels than conventional beta. We were able to classify the beta chain mRNA regulation pathway as primarily involving Fyn, Syk, PI3K, and NFκB. Monomeric IgE is known to greatly increase surface FceRI expression. Interestingly, we found that IgE crosslinkage returned membrane FceRI to basal levels in cells previously incubated with monomeric IgE. Furthermore, the presence of antigen during culture with IgE prevented FceRI upregulation. These data suggest that FceRI signaling not only activates mast cells but may also convey a homeostatic signal returning FceRI expression to a reduced basal level, perhaps to suppress continued signaling. Loss of this suppressive effect could be art of atopic disease etiology. Supported by NIH grants 1R01 AI59638 and U19A1077435.