title: IgE knock-in mice suggest a role for high levels of IgE in basophil-mediated active systemic anaphylaxis.
abstract: Immunoglobulin E (IgE) production is tightly regulated at the cellular and genetic levels and is believed to be central to allergy development. At least two cellular pathways exist that lead to systemic anaphylaxis reactions in vivo: IgE-sensitized mast cells and IgG1-sensitized basophils. Passive anaphylaxis, by application of allergen and allergen-specific antibodies in mice, indicates a differential contribution of immunoglobulin isotypes to anaphylaxis. However, analysis of a dynamic immunization-mediated antibody response in anaphylaxis is difficult. Here, we generated IgE knock-in mice (IgE(ki) ), which express the IgE heavy chain instead of IgG1, in order to analyze the contribution of IgG1 and IgE to active anaphylaxis in vivo. IgE(ki) mice display increased IgE production both in vitro and in vivo. The sensitization of IgE(ki) mice by immunization followed by antigen challenge leads to increased anaphylaxis. Homozygous IgE(ki) mice, which lack IgG1 due to the knock-in strategy, are most susceptible to active systemic anaphylaxis. The depletion of basophils demonstrates their importance in IgE-mediated anaphylaxis. Therefore, we propose that an enhanced, antigen-specific, polyclonal IgE response, as is the case in allergic patients, is probably the most efficient way to sensitize basophils to contribute to systemic anaphylaxis in vivo.
authors: Institute for Immunology, Philipps-Universität Marburg, Marburg, Germany.
authors: Wolger
authors: W
authors: Lübben
authors: Adriana
authors: A
authors: Turqueti-Neves
authors: Anna
authors: A
authors: Okhrimenko
authors: Christian
authors: C
authors: Stöberl
authors: Volker
authors: V
authors: Schmidt
authors: Klaus
authors: K
authors: Pfeffer
authors: Sonja
authors: S
authors: Dehnert
authors: Sarah
authors: S
authors: Wünsche
authors: Silke
authors: S
authors: Storsberg
authors: Stefanie
authors: S
authors: Paul
authors: Stefan
authors: S
authors: Bauer
authors: Gert
authors: G
authors: Riethmüller
authors: David
authors: D
authors: Voehringer
authors: Philipp
authors: P
authors: Yu
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000707:Anaphylaxis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D001491:Basophils / Q000276:immunology* / Q000473:pathology*; D055879:Gene Knock-In Techniques; D006720:Homozygote; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012720:Severity of Illness Index
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin