Background: Asthma is a widespread, multifactorial chronic airway disease. The influence of regulatory B cells on airway hyperreactivity (AHR) and remodeling in asthma is poorly understood.
Objective: Our aim was to analyze the role of B cells in a house dust mite (HDM)-based murine asthma model.
Methods: The influence of B cells on lung function, tissue remodeling, and the immune response were analyzed by using wild-type and B-cell-deficient (μMT) mice and transfer of IL-10-proficient and IL-10-deficient B cells to μMT mice.
Results: After HDM-sensitization, both wild-type and μMT mice developed AHR, but the AHR was significantly stronger in μMT mice, as confirmed by 2 independent techniques: invasive lung function measurement in vivo and examination of 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, whereas the numbers of FoxP3+ and FoxP3- IL-10-secreting regulatory T cells were reduced. Adoptive transfer of IL-10-proficient but not IL-10-deficient B cells into μMT mice before HDM-sensitization attenuated AHR and lung remodeling. In contrast, FoxP3+ regulatory T cells were equally upregulated by transfer of IL-10-proficient and IL-10-deficient B cells.
Conclusion: Our data in a murine asthma model illustrate a central role of regulatory B cells 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.
Keywords: B-cell transfer; Experimental asthma; IL-10; airway hyperreactivity; allergy; house dust mite; lung remodeling; precision-cut lung slices; regulatory B cells.
Copyright © 2020. Published by Elsevier Inc.