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I g E knock‐in mice suggest a role for high levels of I g E in basophil‐mediated active systemic anaphylaxis

2013; Wiley; Volume: 43; Issue: 5 Linguagem: Inglês

10.1002/eji.201242675

1521-4141

Wolger Lübben, Adriana Turqueti‐Neves, Anna Okhrimenko, Christian Stöberl, Volker J. Schmidt, Klaus Pfeffer, Sonja Dehnert, Sarah Wünsche, Silke Storsberg, Stefanie Paul, Stefan Bauer, Gert Riethmüller, David Voehringer, Philipp Yu,

Allergic Rhinitis and Sensitization

Immunglobulin E ( I g E ) 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: I g E ‐sensitized mast cells and I g G 1‐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 I g E knock‐in mice ( I g E ki ), which express the I g E heavy chain instead of I g G 1, in order to analyze the contribution of I g G 1 and I g E to active anaphylaxis in vivo. I g E ki mice display increased I g E production both in vitro and in vivo. The sensitization of I g E ki mice by immunization followed by antigen challenge leads to increased anaphylaxis. Homozygous I g E ki mice, which lack I g G 1 due to the knock‐in strategy, are most susceptible to active systemic anaphylaxis. The depletion of basophils demonstrates their importance in I g E ‐mediated anaphylaxis. Therefore, we propose that an enhanced, antigen‐specific, polyclonal I g E response, as is the case in allergic patients, is probably the most efficient way to sensitize basophils to contribute to systemic anaphylaxis in vivo.