Beutier, H., Gillis, C.M., Iannascoli, B., Godon, O., England, P., Sibilano, R., Reber, L.L., Galli, S.J., Cragg, M.S., Van Rooijen, N., Nancardi, D.A., Bruhns, P. and Jonnson, F. (2016) IgG subclasses determine pathways of anaphylaxis in mice. Journal of Allergy and Clinical Immunology, 1-19. (doi:10.1016/j.jaci.2016.03.028). (PMID:27246523)
Abstract
Background: Animal models have demonstrated that allergen-specific IgG confers sensitivity to systemic anaphylaxis that relies on IgG Fc receptors (Fc?Rs). Mouse IgG2a and IgG2b bind activating Fc?RI, Fc?RIII, and Fc?RIV and inhibitory Fc?RIIB; mouse IgG1 binds only Fc?RIII and Fc?RIIB. Although these interactions are of strikingly different affinities, these 3 IgG subclasses have been shown to enable induction of systemic anaphylaxis.
Objective: We sought to determine which pathways control the induction of IgG1-, IgG2a-, and IgG2b-dependent passive systemic anaphylaxis.
Methods: Mice were sensitized with IgG1, IgG2a, or IgG2b anti-trinitrophenyl mAbs and challenged with trinitrophenyl-BSA intravenously to induce systemic anaphylaxis that was monitored by using rectal temperature. Anaphylaxis was evaluated in mice deficient for Fc?Rs injected with mediator antagonists or in which basophils, monocytes/macrophages, or neutrophils had been depleted. Fc?R expression was evaluated on these cells before and after anaphylaxis.
Results: Activating Fc?RIII is the receptor primarily responsible for all 3 models of anaphylaxis, and subsequent downregulation of this receptor was observed. These models differentially relied on histamine release and the contribution of mast cells, basophils, macrophages, and neutrophils. Strikingly, basophil contribution and histamine predominance in mice with IgG1- and IgG2b-induced anaphylaxis correlated with the ability of inhibitory Fc?RIIB to negatively regulate these models of anaphylaxis.
Conclusion: We propose that the differential expression of inhibitory Fc?RIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass–dependent anaphylaxis. Collectively, our results unravel novel complexities in the involvement and regulation of cell populations in IgG-dependent reactions in vivo.
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