mu-Chain-Deficient Mice Possess B-1 Cells and Produce IgG and IgE, but Not IgA, following Systemic Sensitization and Inhalational Challenge in a Fungal Asthma Model

作者：Ghosh Sumit^*; Hoselton Scott A; Schuh Jane M

来源：The Journal of Immunology, 2012, 189(3): 1322-1329.

DOI：10.4049/jimmunol.1200138

Allergic bronchopulmonary aspergillosis is often difficult to treat and results in morbidity associated with chronic airway changes. This study assessed the requirement for B cells and their products in the allergic pulmonary phenotype in a murine model of fungal allergic asthma that mimics allergic bronchopulmonary aspergillosis. C57BL/6 and mu MT mice (assumed to lack peripheral B cells) were sensitized with Aspergillus fumigatus extract and challenged with two inhalation exposures of live conidia to induce airway disease. Airway hyperresponsiveness after methacholine challenge, peribronchovascular inflammation, goblet cell metaplasia, and fibrotic remodeling of the airways was similar between mu MT mice and their wild-type counterparts (C57BL/6). Surprisingly, even in the absence of the mu-chain, these mu MT mice produced IgE and IgG Abs, although the Abs induced did not have specificity for A. fumigatus Ags. In contrast, IgA was not detected in either the lavage fluid or serum of mu MT mice that had been exposed to A. fumigatus. Our findings also reveal the existence of CD19(+)CD9(+)IgD(+) B-1 cells in the lungs of the mu MT animals. These data show the mMT mice to have a developmental pathway independent of the canonical mu-chain route that allows for their survival upon antigenic challenge with A. fumigatus conidia, although this pathway does not seem to allow for the normal development of Ag-specific repertoires. Additionally, this study shows that IgA is not required for either clearance or containment of A. fumigatus in the murine lung, as fungal outgrowth was not observed in the mu MT animals after multiple inhalation exposures to live conidia. The Journal of Immunology, 2012, 189: 1322-1329.

• 出版日期2012-8-1