Fc receptor β subunit is required for full activation of mast cells through Fc receptor engagement

Abstract

The high-affinity IgE receptor (FcεRI) and the low-affinity IgG receptor (FcγRIII) on mast cells are the key molecules involved in triggering the allergic reaction. These receptors share the common β subunit (FcRβ) which contains an immunoreceptor tyrosine-based activation motif and transduces the signals of these receptors' aggregation. In rodents, FcRβ is essential for the cell surface expression of the FcεRI. In humans, the FcRβ gene was reported to be one of the candidate genes causing atopic diseases. However, the role of FcRβ in vivo still remains ambiguous. To elucidate the functions of FcRβ, we developed the mice lacking FcRβ [FcRβ(-/-)I. The FcRβ(-/-) mice lacked the expression of the FcεRI on mast cells and IgE-mediated passive cutaneous anaphylaxis (PCA) was not induced in FcRβ(-/-) mice as was expected. In these mice, the expression of IgG receptors on mast cells was augmented but the IgG-mediated PCA reaction was attenuated. Although with bone marrow-derived cultured mast cells from FcRβ(-/-), adhesion to fibronectin and Ca2+ flux upon aggregation of IgG receptors were enhanced, mast cells co-cultured with 3T3 fibroblasts exhibited impaired degranulation on receptor aggregation. These observations indicate that FcRβ accelerates the degranulation of mature mast cells via the IgG receptor in connective tissues.