The Role of the FcεRI β-Chain in Allergic DiseasesKraft S. · Rana S. · Jouvin M.-H. · Kinet J.-P.
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass., USA
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Article / Publication Details
The high affinity receptor for IgE, FcΕRI, is a multimeric surface receptor that is expressed exclusively as a tetramer on rodent cells, but exists as a tetramer or trimer on human cells. The tetrameric form is expressed on effector cells of allergic responses such as mast cells and basophils and is composed of an IgE-binding α-subunit, a β-subunit and a γ-subunit dimer. Complexes lacking the β-subunit are found on human antigen-presenting cells. On mast cells and basophils, FcΕRI is essential for IgE-mediated acute allergic reactions. Crosslinking of FcΕRI by IgE and multivalent antigen induces a signaling cascade that culminates in the release of preformed mediators and the synthesis of lipid mediators and cytokines. The β-subunit functions as an amplifier of FcΕRI expression and signaling. As a consequence, strongly enhanced mast cell effector functions and in vivo allergic reactions can be observed in the presence of FcΕRIβ. In contrast, a truncated β-isoform (βT) that is produced by alternative splicing acts as an inhibitor of FcΕRI surface expression. Thus, by producing two proteins with antagonistic functions, the FcΕRIβ gene could serve as a potent regulator of allergic responses. In addition, the genomic region encompassing the β-chain has been linked to atopy and a number of polymorphisms within the FcΕRIβ gene are associated with various atopic diseases. It remains to be elucidated how these polymorphisms might affect the allergic phenotype. These functions of the β-chain together with the described genetic linkages to atopy make it a candidate for a role in the pathophysiology of allergic diseases.
© 2004 S. Karger AG, Basel
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