Regulatory B cells control airway hyperreactivity and lung remodeling in a murine asthma model

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 (& micro;MT) mice and transfer of IL-10-proficient and IL-10-deficient B cells to & micro;MT mice. Results: After HDM-sensitization, both wild-type and & micro;MT mice developed AHR, but the AHR was significantly stronger in & micro;MT 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 & micro;MT 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 & micro;MT 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. (J Allergy Clin Immunol 2021;147:2281-94.)