title: In vivo effector functions of high-affinity mouse IgG receptor FcγRI in disease and therapy models.
abstract: Two activating mouse IgG receptors (FcγRs) have the ability to bind monomeric IgG, the high-affinity mouse FcγRI and FcγRIV. Despite high circulating levels of IgG, reports using FcγRI-/-or FcγRIV-/-mice or FcγRIV-blocking antibodies implicate these receptors in IgG-induced disease severity or therapeutic Ab efficacy. From these studies, however, one cannot conclude on the effector capabilities of a given receptor, because different activating FcγRs possess redundant properties in vivo, and cooperation between FcγRs may occur, or priming phenomena. To help resolve these uncertainties, we used mice expressing only FcγRI to determine its intrinsic properties in vivo. FcγRIonlymice were sensitive to IgG-induced autoimmune thrombocytopenia and anti-CD20 and anti-tumour immunotherapy, but resistant to IgG-induced autoimmune arthritis, anaphylaxis and airway inflammation. Our results show that the in vivo roles of FcγRI are more restricted than initially reported using FcγRI-/-mice, but confirm effector capabilities for this high-affinity IgG receptor in vivo.
authors.affiliation: Institut Pasteur, Department of Immunology, Unit of Antibodies in Therapy and Pathology, 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: Institut Pasteur, Department of Immunology, Unit of Antibodies in Therapy and Pathology, Paris, France; INSERM U1222, Paris, France.
authors.forename: Priscila P
authors.initials: PP
authors.lastname: Zenatti
authors.affiliation: Institut Pasteur, Department of Immunology, Unit of Antibodies in Therapy and Pathology, Paris, France; INSERM U1222, Paris, France.
authors.forename: David A
authors.initials: DA
authors.lastname: Mancardi
authors.affiliation: Institut Pasteur, Department of Immunology, Unit of Antibodies in Therapy and Pathology, Paris, France; INSERM U1222, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Héloïse
authors.initials: H
authors.lastname: Beutier
authors.affiliation: Département Infection et Epidémiologie, Unité d'Histopathologie Humaine et Modèles Animaux, Institut Pasteur, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiette
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Macdonald
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.affiliation: Institut Pasteur, Dynamics of Immune Responses Unit, 75015 Paris, France; INSERM U1223, rue du Dr Roux, Paris, France.
authors.forename: Susanna
authors.initials: S
authors.lastname: Celli
authors.affiliation: Institut Pasteur, Dynamics of Immune Responses Unit, 75015 Paris, France; INSERM U1223, rue du Dr Roux, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bousso
authors.affiliation: Institut Pasteur, Department of Immunology, Unit of Antibodies in Therapy and Pathology, Paris, France; INSERM U1222, Paris, France.
authors.forename: Friederike
authors.initials: F
authors.lastname: Jönsson
authors.affiliation: Institut Pasteur, Department of Immunology, Unit of Antibodies in Therapy and Pathology, Paris, France; INSERM U1222, Paris, France. Electronic address: bruhns@pasteur.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bruhns
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use*; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006498:Hepatectomy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology* / Q000628:therapy; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D013156:Splenectomy
chemical_list: D019138:Antibodies, Blocking; C485701:Fcgr1 protein, mouse; D017452:Receptors, IgG
keywords: Fc receptors; IgG-induced pathologies; Immunotherapy; Mouse models