Document Detail


IgE knock-in mice suggest a role for high levels of IgE in basophil-mediated active systemic anaphylaxis.
MedLine Citation:
PMID:  23423996     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Wolger Lübben; Adriana Turqueti-Neves; Anna Okhrimenko; Christian Stöberl; Volker Schmidt; Klaus Pfeffer; Sonja Dehnert; Sarah Wünsche; Silke Storsberg; Stefanie Paul; Stefan Bauer; Gert Riethmüller; David Voehringer; Philipp Yu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-27
Journal Detail:
Title:  European journal of immunology     Volume:  43     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-25     Completed Date:  2013-06-17     Revised Date:  2013-10-29    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1231-42     Citation Subset:  IM    
Copyright Information:
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Institute for Immunology, Philipps-Universität Marburg, Marburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Allergens / administration & dosage,  immunology
Anaphylaxis / genetics,  immunology*,  pathology*
Animals
Antibodies, Monoclonal / biosynthesis,  immunology
Basophils / immunology*,  pathology*
Gene Knock-In Techniques
Homozygote
Humans
Immunization
Immunoglobulin E / genetics,  immunology*
Immunoglobulin G / genetics,  immunology*
Mast Cells / immunology,  pathology
Mice
Ovalbumin / administration & dosage,  immunology
Severity of Illness Index
Grant Support
ID/Acronym/Agency:
241506//European Research Council
Chemical
Reg. No./Substance:
0/Allergens; 0/Antibodies, Monoclonal; 0/Immunoglobulin G; 37341-29-0/Immunoglobulin E; 9006-59-1/Ovalbumin
Comments/Corrections
Erratum In:
Eur J Immunol. 2013 Apr;43(5):1389-90

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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