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

Abstract：

BACKGROUND: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. OBJECTIVE:We now sought to determine whether the confinement to a single D(H) gene segment alone leads to a reduced allergic phenotype. METHODS: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. RESULTS: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. CONCLUSION: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.

journal_name

Int Arch Allergy Immunol

journal_title

International archives of allergy and immunology

authors

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

doi

10.1159/000323527

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

247-58

issue

eissn

1018-2438

issn

1423-0097

pii

000323527

journal_volume

156

pub_type

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