Inducible bronchus-associated lymphoid tissue (iBALT) in patients with pulmonary complications of rheumatoid arthritis

J Clin Invest. 2006 Dec;116(12):3183-94. doi: 10.1172/JCI28756.


Bronchus-associated lymphoid tissue (BALT) was originally described as a mucosal lymphoid organ in the lungs of some species. However, while the lungs of naive mice and humans typically lack BALT, pulmonary infection in mice leads to the development of inducible BALT (iBALT), which is located in peribronchial, perivascular, and interstitial areas throughout the lung. Here we investigated whether iBALT forms in patients with a variety of interstitial lung diseases. We show that while iBALT can be found in the lungs of patients suffering from multiple diseases, well-developed iBALT is most prevalent in patients with pulmonary complications of RA and Sjögren syndrome. In these patients, iBALT consisted of numerous B cell follicles containing germinal centers and follicular dendritic cells. A loosely defined T cell area surrounded the B cell follicles while lymphatics and high endothelial venules were found at the B cell/T cell interface. Increased expression of lymphoid-organizing chemokines, such as CXCL13 and CCL21, as well as molecules involved in the immunopathology of RA, such as B cell-activating factor of the TNF family (BAFF), ICOS ligand, and lymphotoxin, correlated with more well-developed iBALT. Finally, the presence of iBALT correlated with tissue damage in the lungs of RA patients, suggesting that iBALT participates in local RA pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Autoantibodies / analysis
  • Cell Aggregation
  • Chemokines / genetics
  • Chemokines / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression / genetics
  • Humans
  • Immunohistochemistry
  • Lung / metabolism*
  • Lung / pathology
  • Lung Diseases, Interstitial / complications
  • Lung Diseases, Interstitial / immunology
  • Lung Diseases, Interstitial / metabolism*
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism*
  • Lymphoid Tissue / pathology
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sjogren's Syndrome / complications
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / metabolism


  • Autoantibodies
  • Chemokines
  • Cytokines
  • RNA, Messenger