BACKGROUND: Asthma is a widespread, multifactorial chronic airway disease. The influence of regulatory B cells (Bregs) on airway hyperreactivity (AHR) and remodeling in asthma is poorly understood. OBJECTIVE: We analyzed the role of B cells in a house dust mite (HDM)-based murine asthma model. METHODS: By employing wildtype (WT) and B cell-deficient (μMT) mice and transfer of IL-10-proficient and IL-10-deficient B cells to μMT mice, the influence of B cells on lung function, tissue remodeling and the immune response was analyzed. RESULTS: After HDM-sensitization, both WT and μMT mice developed AHR, but AHR was significantly stronger in μMT mice as confirmed by two independent techniques: invasive lung function measurement in vivo and precision-cut lung slices ex vivo. Moreover, airway remodeling was significantly increased in allergic μMT mice as shown by enhanced collagen deposition in the airways, while regulatory FoxP3(+) and FoxP3(-) IL-10-secreting T cells (Tregs) were reduced. Adoptive transfer of IL-10-proficient, but not IL-10-deficient B cells into μMT mice prior to HDM-sensitization, attenuated AHR and lung remodeling. In contrast, FoxP3(+) Tregs were equally upregulated by transfer of IL-10-proficient as well as IL-10-deficient B cells. CONCLUSION: Our data in a murine asthma model illustrate a central role of Bregs in the control of lung function and airway remodeling, and may support future concepts for B cell targeted prevention and treatment strategies for allergic asthma.
- Dipl-Biol, A. H.
- Happle, C.
- Grychtol, R. M.
- Skuljec, J.
- Busse, M.
- Dalüge, K.
- Obernolte, H.
- Sewald, K.
- Braun, A.
- Meyer-Bahlburg, A.
- Hansen, G.
Keywords
- B cell transfer
- Il-10
- airway hyperreactivity
- allergy
- experimental asthma
- house dust mite
- lung remodeling
- precision-cut lung slices
- regulatory B cells