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 (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.