Supplementary Material for: A Single D<sub>H</sub> Gene Segment Is Sufficient for the Establishment of an Asthma Phenotype in a Murine Model of Allergic Airway Inflammation
2011-06-29T00:00:00Z (GMT) by
<i>Background:</i> 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 <i>Diversity</i> gene segment (D<sub>H</sub>) 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. <i>Objective:</i> We now sought to determine whether the confinement to a single D<sub>H</sub> gene segment alone leads to a reduced allergic phenotype. <i>Methods:</i> We examined another gene-targeted mouse strain (ΔD-DFL) with a single D<sub>H</sub> gene segment which encodes for neutral amino acids, thus reflecting the preferential repertoire in wild-type mice. Mice were sensitized intraperitoneally to ovalbumin. <i>Results:</i> Despite the constraint to a single D<sub>H</sub> gene segment, ΔD-DFL mice mounted high total and allergen-specific IgG<sub>1</sub> and IgE serum levels after sensitization to ovalbumin. The affinity constants of allergen-specific IgG<sub>1</sub> antibodies did not differ between ΔD-DFL and wild type. Following challenge with aerosolized allergen, a marked local T<sub>H</sub>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. <i>Conclusion:</i> A single D<sub>H</sub> 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.