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J Allergy Clin Immunol. 2017 Jan;139(1):269-280.e7. doi: 10.1016/j.jaci.2016.03.028. Epub 2016 Apr 26.

IgG subclasses determine pathways of anaphylaxis in mice.

Author information

1
Department of Immunology, Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France; INSERM, U1222, Paris, France; Université Pierre et Marie Curie, Paris, France.
2
Department of Immunology, Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France; INSERM, U1222, Paris, France.
3
Institut Pasteur, Plate-Forme de Biophysique Moléculaire, Centre d'Innovation et Recherche Technologique (CiTech), CNRS-UMR3528, Paris, France.
4
Department of Pathology, Stanford University School of Medicine, Stanford, Calif; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif.
5
Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, United Kingdom.
6
Department of Molecular Cell Biology, VU Medical Center, Amsterdam, The Netherlands.
7
Department of Immunology, Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France; INSERM, U1222, Paris, France. Electronic address: bruhns@pasteur.fr.
8
Department of Immunology, Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France; INSERM, U1222, Paris, France. Electronic address: joensson@pasteur.fr.

Abstract

BACKGROUND:

Animal models have demonstrated that allergen-specific IgG confers sensitivity to systemic anaphylaxis that relies on IgG Fc receptors (FcγRs). Mouse IgG2a and IgG2b bind activating FcγRI, FcγRIII, and FcγRIV and inhibitory FcγRIIB; mouse IgG1 binds only FcγRIII and FcγRIIB. 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 FcγRs injected with mediator antagonists or in which basophils, monocytes/macrophages, or neutrophils had been depleted. FcγR expression was evaluated on these cells before and after anaphylaxis.

RESULTS:

Activating FcγRIII 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 FcγRIIB to negatively regulate these models of anaphylaxis.

CONCLUSION:

We propose that the differential expression of inhibitory FcγRIIB 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.

KEYWORDS:

Anaphylaxis; IgG; IgG Fc receptor; basophil; histamine; macrophage; monocyte; mouse model; neutrophil; platelet-activating factor

PMID:
27246523
PMCID:
PMC5081282
DOI:
10.1016/j.jaci.2016.03.028
[Indexed for MEDLINE]
Free PMC Article

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