Allergy-associated FcRbeta is a molecular amplifier of IgE- and IgG-mediated in vivo responses.
A role for the Fc receptor beta chain (FcRbeta) in the pathogenesis of allergy has been suggested by genetic studies. FcRbeta is a subunit common to the high-affinity IgE (FcepsilonRI) and low-affinity IgG (FcgammaRIII) receptors, both of which contribute to the initiation of allergic reactions. Current in vitro data suggest that FcRbeta can function as either a positive or negative regulator, leaving a mechanistic explanation for its association with the development of atopy unclear. To address this controversy, we have generated novel mouse models relevant to human Fc receptor function. Analysis of FcepsilonRI- and FcgammaRIII-dependent responses in these mice provides unequivocal genetic evidence that FcRbeta functions as an amplifier of early and late mast cell responses and, remarkably, in vivo anaphylactic responses.
Dombrowicz
D
D
Laboratory of Allergy and Immunology, Beth Israel Deaconess Medical Center, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02215, USA.
Lin
S
S
Flamand
V
V
Brini
A T
AT
Koller
B H
BH
Kinet
J P
JP
D000707:Anaphylaxis / Q000209:etiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D007073:Immunoglobulin E / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D010766:Phosphorylation; D017455:Receptors, IgE / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D007074:Immunoglobulin G; D015850:Interleukin-6; D017455:Receptors, IgE; D017452:Receptors, IgG; D007073:Immunoglobulin E; D002118:Calcium