B-Cell Activating Factor Secreted by Neutrophils Is a Critical Player in Lung Inflammation to Cigarette Smoke Exposure

Front Immunol. 2020 Jul 29;11:1622. doi: 10.3389/fimmu.2020.01622. eCollection 2020.


Cigarette smoke (CS) is the major cause of chronic lung injuries, such as chronic obstructive pulmonary disease (COPD). In patients with severe COPD, tertiary lymphoid follicles containing B lymphocytes and B cell-activating factor (BAFF) overexpression are associated with disease severity. In addition, BAFF promotes adaptive immunity in smokers and mice chronically exposed to CS. However, the role of BAFF in the early phase of innate immunity has never been investigated. We acutely exposed C57BL/6J mice to CS and show early BAFF expression in the bronchoalveolar space and lung tissue that correlates to airway neutrophil and macrophage influx. Immunostaining analysis revealed that neutrophils are the major source of BAFF. We confirmed in vitro that neutrophils secrete BAFF in response to cigarette smoke extract (CSE) stimulation. Antibody-mediated neutrophil depletion significantly dampens lung inflammation to CS exposure but only partially decreases BAFF expression in lung tissue and bronchoalveolar space suggesting additional sources of BAFF. Importantly, BAFF deficient mice displayed decreased airway neutrophil recruiting chemokines and neutrophil influx while the addition of exogenous BAFF significantly enhanced this CS-induced neutrophilic inflammation. This demonstrates that BAFF is a key proinflammatory cytokine and that innate immune cells in particular neutrophils, are an unconsidered source of BAFF in early stages of CS-induced innate immunity.

Keywords: B cell activating factor; cigarette smoke; mice; neutrophils; pulmonary inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Cell Activating Factor / biosynthesis*
  • B-Cell Activating Factor / genetics
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Susceptibility
  • Gene Expression
  • Humans
  • Inflammation Mediators / metabolism
  • Inhalation Exposure / adverse effects*
  • Male
  • Mice
  • Neutrophil Infiltration
  • Neutrophils / immunology*
  • Neutrophils / metabolism*
  • Pneumonia / etiology*
  • Pneumonia / metabolism*
  • Pneumonia / pathology
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Tobacco Smoke Pollution / adverse effects*
  • Tobacco Smoking / adverse effects


  • B-Cell Activating Factor
  • Cytokines
  • Inflammation Mediators
  • Tobacco Smoke Pollution