μ-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.
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 μMT 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 μMT mice and their wild-type counterparts (C57BL/6). Surprisingly, even in the absence of the μ-chain, these μMT 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 μMT 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 μMT animals. These data show the μMT mice to have a developmental pathway independent of the canonical μ-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 μMT animals after multiple inhalation exposures to live conidia.
Department of Veterinary and Microbiological Sciences, North Dakota State University, Fargo, ND 58108, USA. Sumit.Ghosh@ndsu.edu
Sumit
S
Ghosh
Scott A
SA
Hoselton
Jane M
JM
Schuh
D000280:Administration, Inhalation; D000818:Animals; D000946:Antigens, Fungal / Q000008:administration & dosage* / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007114:Immunization / Q000379:methods; D007070:Immunoglobulin A; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D055732:Pulmonary Aspergillosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D000946:Antigens, Fungal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007148:Immunoglobulin mu-Chains; D007073:Immunoglobulin E