title: IgG subclasses determine pathways of anaphylaxis in mice.
abstract: Animal models have demonstrated that allergen-specific IgG confers sensitivity to systemic anaphylaxis that relies on IgG Fc receptors (FcγRs). Mouse IgG2aand IgG2bbind activating FcγRI, FcγRIII, and FcγRIV and inhibitory FcγRIIB; mouse IgG1binds 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.
  
  
  
  We sought to determine which pathways control the induction of IgG1-, IgG2a-, and IgG2b-dependent passive systemic anaphylaxis.
  
  
  
  Mice were sensitized with IgG1, IgG2a, or IgG2banti-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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Héloïse
authors.initials: H
authors.lastname: Beutier
authors.affiliation: 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.
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Gillis
authors.affiliation: Department of Immunology, Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France; INSERM, U1222, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Iannascoli
authors.affiliation: Department of Immunology, Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France; INSERM, U1222, Paris, France.
authors.forename: Ophélie
authors.initials: O
authors.lastname: Godon
authors.affiliation: Institut Pasteur, Plate-Forme de Biophysique Moléculaire, Centre d'Innovation et Recherche Technologique (CiTech), CNRS-UMR3528, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: England
authors.affiliation: 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.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sibilano
authors.affiliation: Department of Immunology, Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France; INSERM, U1222, Paris, France.
authors.forename: Laurent L
authors.initials: LL
authors.lastname: Reber
authors.affiliation: 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.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
authors.affiliation: Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, United Kingdom.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cragg
authors.affiliation: Department of Molecular Cell Biology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.affiliation: Department of Immunology, Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France; INSERM, U1222, Paris, France.
authors.forename: David A
authors.initials: DA
authors.lastname: Mancardi
authors.affiliation: Department of Immunology, Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France; INSERM, U1222, Paris, France. Electronic address: bruhns@pasteur.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bruhns
authors.affiliation: Department of Immunology, Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France; INSERM, U1222, Paris, France. Electronic address: joensson@pasteur.fr.
authors.forename: Friederike
authors.initials: F
authors.lastname: Jönsson
mesh_terms: D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D006241:Haptens / Q000276:immunology; D006632:Histamine / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology; D021122:Protein Subunits / Q000276:immunology*; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D006241:Haptens; D007074:Immunoglobulin G; D021122:Protein Subunits; D017452:Receptors, IgG; C038601:trinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E; D006632:Histamine
keywords: Anaphylaxis; IgG; IgG Fc receptor; basophil; histamine; macrophage; monocyte; mouse model; neutrophil; platelet-activating factor