Fungal aeroallergen challenge results in increased granulocytic inflammation in Jh-/- mice in a murine model of allergic airway disease (HYP7P.280)

Abstract

Abstract B lymphocytes are well recognized in the development of IgE responses, which exacerbates asthma symptoms, but may also be important as a protective response against inhaled fungi. Further, these lymphocytes may play a direct role in the maintenance of airway wall fibrosis. Jh-/- mice have been used extensively to study the role of B lymphocytes in immune responses. These mice lack the Jh gene, which codes for the antibody heavy chain and is thought to be critical for B cell survival and function. In this study, we examined the role of B lymphocytes using a murine fungal aeroallergen model to mimic human fungal allergic airway disease. We compared disease progression in the BALB/c and Jh-/- mice and found no differences in airway hyperresponsiveness, collagen deposition, or overall pulmonary inflammation. However, the Jh-/- mice had a significantly higher number of neutrophils and eosinophils when compared to the BALB/c mice. IL-17A and IL-6 cytokines, which play a role in driving eosinophilia and neutrophilia, were also significantly higher in the Jh-/- mice after fungal challenge. We plan to characterize temporal activation and the relative contribution of these B lymphocytes in the maintenance of Tregs and Th17 lymphocytes within the pulmonary compartment. These studies will help expand our knowledge of how B lymphocytes regulate T lymphocyte responses in allergic asthma.