Role of B cells in T_H cell responses in a mouse model of asthma.

Abstract

The importance of B lymphocytes to present antigens for antibody production is well documented. In contrast, very little is known about their capacity to influence CD4⁺ T-cell activation during a primary or secondary response to allergens. Using mouse models of asthma, we investigated the role of B cells as antigen-presenting cells in priming and maintenance of T_H cell responses. Mice were immunized through the intranasal route with house dust mite (HDM) extract derived from Dermatophagoides pteronyssinus. B cells were depleted in HDM-sensitized animals to investigate the importance of B cells in maintenance of the allergic response. B cells were depleted before HDM sensitization to investigate the role of B cells in T-cell priming; furthermore, HDM sensitization was performed in mice with MHC class II expression restricted to the B-cell lineage. We found that B cells serve as potent antigen-presenting cells ex vivo and restimulate in vivo-primed HDM-specific T_H cells. HDM antigens were taken up by B cells independently of B-cell receptor specificity, indicating that HDM uptake and antigen presentation to CD4⁺ T cells is not restricted to rare B cells carrying HDM-specific B cell receptors. B-cell depletion before HDM challenge in HDM-sensitized mice resulted in a dramatic reduction of allergic response, indicating the role of B cells in amplification of T_H2 responses. In contrast, HDM sensitization of mice in which MHC class II expression was restricted to B cells revealed the inability of these cells to prime T_H2 responses but highlighted their unexpected role in priming T_H1 and T_H17 responses. Collectively, these data reveal new mechanisms leading to initiation and exacerbation of the allergic response that might have implications for designing new therapeutic strategies to combat HDM allergy.