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

J Allergy Clin Immunol. 2021 Jun;147(6):2281-2294.e7. doi: 10.1016/j.jaci.2020.09.041. Epub 2020 Nov 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Remodeling / immunology*
  • Allergens / immunology
  • Animals
  • Asthma / etiology*
  • Asthma / metabolism*
  • Asthma / pathology
  • B-Lymphocytes, Regulatory / immunology*
  • B-Lymphocytes, Regulatory / metabolism*
  • Biomarkers
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / metabolism
  • Bronchial Hyperreactivity / pathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Susceptibility
  • Lymphocyte Activation
  • Mice
  • Pyroglyphidae / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism


  • Allergens
  • Biomarkers
  • Cytokines