Tobias Rogosch - A single DH gene segment is sufficient for the establishment of an asthma phenotype in a murine model of allergic airway inflammation.

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  Publication Details (including relevant citation   information):

  Kerzel S,   Rogosch T, Wagner J, Preisser K, Yildirim AÖ, Fehrenbach H, Garn   H, Maier RF, Schroeder HW Jr, Zemlin M.

  Int Arch   Allergy Immunol. 2011;156(3):247-58.

  doi: 10.1159/000323527



  We have previously shown that the allergic sensitization to   ovalbumin does not represent a superantigen-like immune response.   In gene-targeted mice (ΔD-iD) with a single modified Diversity   gene segment (D(H)) of the immunoglobulin heavy chain, enriched   for charged amino acids, the asthma phenotype in a murine model   was markedly alleviated compared to wild-type animals.


  We now sought to determine whether the confinement to a single   D(H) gene segment alone leads to a reduced allergic phenotype.


  We examined another gene-targeted mouse strain (ΔD-DFL) with a   single D(H) gene segment which encodes for neutral amino acids,   thus reflecting the preferential repertoire in wild-type mice.   Mice were sensitized intraperitoneally to ovalbumin.


  Despite the constraint to a single D(H) gene segment, ΔD-DFL mice   mounted high total and allergen-specific IgG(1) and IgE serum   levels after sensitization to ovalbumin. The affinity constants   of allergen-specific IgG(1) antibodies did not differ between   ΔD-DFL and wild type. Following challenge with aerosolized   allergen, a marked local T(H)2 cytokine response and an   eosinophilic airway inflammation developed. Quantitative   histology revealed increased mucus production and intense goblet   cell metaplasia which were identical to those in wild type.   Moreover, ΔD-DFL mice developed an airway hyperreactivity to   methacholine and to the specific allergen, which both did not   differ from those in wild-type animals.


  A single D(H) gene segment is sufficient for the establishment of   the asthma phenotype in a murine model of allergic airway   inflammation. Thus, the allergic phenotype depends on the amino   acid composition and not on the diversity of the classical   antigen-binding site.

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