Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD

Am J Physiol Lung Cell Mol Physiol. 2014 Nov 1;307(9):L692-706. doi: 10.1152/ajplung.00092.2014. Epub 2014 Aug 15.


Chronic obstructive pulmonary disease (COPD) is characterized by a progressive decline in lung function, caused by exposure to exogenous particles, mainly cigarette smoke (CS). COPD is initiated and perpetuated by an abnormal CS-induced inflammatory response of the lungs, involving both innate and adaptive immunity. Specifically, B cells organized in iBALT structures and macrophages accumulate in the lungs and contribute to CS-induced emphysema, but the mechanisms thereof remain unclear. Here, we demonstrate that B cell-deficient mice are significantly protected against CS-induced emphysema. Chronic CS exposure led to an increased size and number of iBALT structures, and increased lung compliance and mean linear chord length in wild-type (WT) but not in B cell-deficient mice. The increased accumulation of lung resident macrophages around iBALT and in emphysematous alveolar areas in CS-exposed WT mice coincided with upregulated MMP12 expression. In vitro coculture experiments using B cells and macrophages demonstrated that B cell-derived IL-10 drives macrophage activation and MMP12 upregulation, which could be inhibited by an anti-IL-10 antibody. In summary, B cell function in iBALT formation seems necessary for macrophage activation and tissue destruction in CS-induced emphysema and possibly provides a new target for therapeutic intervention in COPD.

Keywords: B cells; COPD; IL-10; iBALT; macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Cell Movement
  • Coculture Techniques
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Interleukin-10 / antagonists & inhibitors
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Macrophage Activation*
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Matrix Metalloproteinase 12 / genetics
  • Matrix Metalloproteinase 12 / metabolism*
  • Mice
  • Mice, Knockout
  • Pancreatic Elastase
  • Pulmonary Disease, Chronic Obstructive / chemically induced
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Emphysema / chemically induced
  • Pulmonary Emphysema / immunology*
  • Pulmonary Emphysema / metabolism
  • Pulmonary Emphysema / pathology
  • Respiratory Function Tests
  • Tobacco Smoke Pollution / adverse effects*


  • Antibodies
  • Tobacco Smoke Pollution
  • Interleukin-10
  • Pancreatic Elastase
  • Matrix Metalloproteinase 12