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

The high-affinity IgE receptor (Fc epsilon RI) and the low-affinity IgG receptor (Fc gamma RIII) on mast cells are the key molecules involved in triggering the allergic reaction. These receptors share the common beta subunit (FcR beta) which contains an immunoreceptor tyrosine-based activation motif and transduces the signals of these receptors' aggregation. In rodents, FcR beta is essential for the cell surface expression of the Fc epsilon RI, In humans, the FcR beta gene was reported to be one of the candidate genes causing atopic diseases. However, the role of FcR beta in vivo still remains ambiguous. To elucidate the functions of FcR beta, we developed the mice lacking FcR beta [FcR beta(-/-)]. The FcR beta(-/-) mice lacked the expression of the Fc epsilon RI on mast cells and IgE-mediated passive cutaneous anaphylaxis (PCA) was not induced in FcR beta(-/-) 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 FcR beta(-/-), 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 FcR beta accelerates the degranulation of mature mast cells via the IgG receptor in connective tissues.