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

作者:Dullaers Melissa; Schuijs Martijn J; Willart Monique; Fierens Kaat; Van Moorleghem Justine; Hammad Hamida; Lambrecht Bart N*
来源:Journal of Allergy and Clinical Immunology, 2017, 140(1): 76-+.
DOI:10.1016/j.jaci.2016.09.020

摘要

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. InvivoBcellswere dispensable for activation of naive 1-DERTcells but necessary for full expansion of primed 1-DER T cells. At high HDMchallenge doses, Bcells were not required for development of pulmonary asthmatic features yet contributed to T(H)2 expansion in themediastinal lymph nodes but not in the lungs. When theamount 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.

  • 出版日期2017-7