The role of the FcepsilonRI beta-chain in allergic diseases.
The high affinity receptor for IgE, FcepsilonRI, 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 alpha-subunit, a beta-subunit and a gamma-subunit dimer. Complexes lacking the beta-subunit are found on human antigen-presenting cells. On mast cells and basophils, FcepsilonRI is essential for IgE-mediated acute allergic reactions. Crosslinking of FcepsilonRI 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 beta-subunit functions as an amplifier of FcepsilonRI expression and signaling. As a consequence, strongly enhanced mast cell effector functions and in vivo allergic reactions can be observed in the presence of FcepsilonRIbeta. In contrast, a truncated beta-isoform (betaT) that is produced by alternative splicing acts as an inhibitor of FcepsilonRI surface expression. Thus, by producing two proteins with antagonistic functions, the FcepsilonRIbeta gene could serve as a potent regulator of allergic responses. In addition, the genomic region encompassing the beta-chain has been linked to atopy and a number of polymorphisms within the FcepsilonRIbeta gene are associated with various atopic diseases. It remains to be elucidated how these polymorphisms might affect the allergic phenotype. These functions of the beta-chain together with the described genetic linkages to atopy make it a candidate for a role in the pathophysiology of allergic diseases.
Kraft
Stefan
S
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Rana
Shalini
S
Jouvin
Marie-Hélène
MH
Kinet
Jean-Pierre
JP
D000818:Animals; D015870:Gene Expression; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D011110:Polymorphism, Genetic / Q000235:genetics / Q000276:immunology; D017455:Receptors, IgE / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D015398:Signal Transduction
D007074:Immunoglobulin G; D017455:Receptors, IgE; D007073:Immunoglobulin E