House dust mite–driven asthma and allergen-specific T cells depend on B cells when the amount of inhaled allergen is limiting

Background Allergic asthma is a CD4 T H 2-lymphocyte driven disease characterized by airway hyperresponsiveness and eosinophilia. B cells can present antigens to CD4 T cells and produce IgE immunoglobulins that arm effector cells; however, mouse models are inconclusive on whether B cells are necessary for asthma development. Objectives We sought to address the role of B cells in a house dust mite (HDM)–driven T H 2-high asthma mouse model. Methods Wild-type and B cell–deficient muMT mice were sensitized and challenged through the airways with HDM extracts. The antigen-presenting capacities of B cells were studied by using new T-cell receptor transgenic 1-DER mice specific for the Der p 1 allergen. Results In vitro –activated B cells from HDM-exposed mice presented antigen to 1-DER T cells and induced a T H 2 phenotype. In vivo B cells were dispensable for activation of naive 1-DER T cells but necessary for full expansion of primed 1-DER T cells. At high HDM challenge doses, B cells were not required for development of pulmonary asthmatic features yet contributed to T H 2 expansion in the mediastinal lymph nodes but not in the lungs. When the amount of challenge allergen was decreased, muMT mice had reduced asthma features. Under these limiting conditions, B cells contributed also to expansion of T H 2 effector cells in the lungs and central memory T cells in the mediastinal lymph nodes. Conclusion B cells are a major part of the adaptive immune response to inhaled HDM allergen, particularly when the amount of inhaled allergen is low, by expanding allergen-specific T cells.