Multiple functions for the β subunit of FcεRI: positive and negative regulation of human mast cell activation, survival, and proliferation

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIAID	IMMUNO/INFLAM-3

Authors

• G Cruse
• A Gilfillan
• M Beaven
• D Metcalfe

Abstract

FcεRI on mast cells consists of an IgE-binding α subunit, two γ chains which initiate signaling and a β subunit which, in mice, has been proposed to potentiate FcεRIγ-mediated signaling. However, the function of the β subunit in human mast cells is unknown. We recently identified a novel variant of FcεRIβ in human mast cells which lacks exon 3 and may regulate survival and proliferation. In this study, we used shRNA targeting exon 3 to knockdown just full length FcεRIβ (KDv1) and exon 1 to knockdown both variants of FcεRIβ (KDv2). Both versions reduced surface expression of FcεRIα and attenuated antigen-induced mast cell degranulation. Interestingly, C3a-induced degranulation was augmented following FcεRIβ knockdown with KDv1. Similarly, receptor-independent thapsigargin-induced calcium influx and IL-8 production were augmented with KDv1 compared to scrambled control. Degranulation and IL-8 production induced by thapsigargin were inhibited following KDv2 treatment but no difference was evident with calcium influx or PGD2 release. KDv1 induced mast cell apoptosis, whilst KDv2 did not induce apoptosis but reduced the number of cells in G2 phase. Thus FcεRIβ variants may have opposing roles in mast cell survival and activation suggesting that skewed expression of these variants may contribute to altered mast cell function.

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