title: B Cell-Activating Factor. An Orchestrator of Lymphoid Follicles in Severe Chronic Obstructive Pulmonary Disease.
abstract: BACKGROUND
  Patients with chronic obstructive pulmonary disease (COPD) have increased pulmonary lymphoid follicle (LF) counts. B cell-activating factor of tumor necrosis factor family (BAFF) regulates B cells in health, but its role in COPD pathogenesis is unclear.
  
  
  OBJECTIVE
  To determine whether BAFF expression in pulmonary LFs correlates with COPD severity, LF size or number, and/or readouts of B-cell function in LFs.
  
  
  METHODS
  We correlated BAFF immunostaining in LFs in lung explants or biopsies from nonsmoking control subjects (NSC), smokers without COPD (SC), and patients with COPD with the number and size of LFs, and LF B-cell apoptosis, activation, and proliferation. We analyzed serum BAFF levels and BAFF expression in B cells in blood and bronchoalveolar lavage samples from the same subject groups. We assessed whether: (1) cigarette smoke extract (CSE) increases B-cell BAFF expression and (2) recombinant BAFF (rBAFF) rescues B cells from CSE-induced apoptosis by inhibiting activation of nuclear factor-κB (NF-κB).
  
  
  RESULTS
  Patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD had increased numbers and larger pulmonary LFs than patients with GOLD stages I-II COPD and SC. We identified two main types of pulmonary LFs: (1) type A, the predominant type in GOLD stages I-II COPD and SC, characterized by abundant apoptotic but few BAFF-positive cells (mostly B cells); and (2) type B, the main type in GOLD stage IV COPD, characterized by abundant BAFF-positive cells but few apoptotic cells (mostly B cells). BAFF levels were also higher in blood and bronchoalveolar lavage B cells in patients with COPD versus NSC and SC. Surprisingly, rBAFF blocked CSE-induced B-cell apoptosis by inhibiting CSE-induced NF-κB activation.
  
  
  CONCLUSIONS
  Our data support the hypothesis that B-cell BAFF expression creates a self-perpetuating loop contributing to COPD progression by promoting pulmonary B-cell survival and LF expansion.
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine and.|2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.|3 University of Parma, Parma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Polverino
authors.affiliation: 4 Research Unit, FISIB, IdISPa, and.|5 Department of Respiratory Medicine, Hospital Son Espases, Ciber de Enfermedades Respiratorias (CIBERES), Mallorca, Spain.
authors.forename: Borja G
authors.initials: BG
authors.lastname: Cosio
authors.affiliation: 4 Research Unit, FISIB, IdISPa, and.|6 Immunology Department, Hospital Son Espases, Mallorca, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Pons
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine and.
authors.forename: Maria
authors.initials: M
authors.lastname: Laucho-Contreras
authors.affiliation: 7 Harvard School of Public Health, Boston, Massachusetts; and.
authors.forename: Paula
authors.initials: P
authors.lastname: Tejera
authors.affiliation: 4 Research Unit, FISIB, IdISPa, and.
authors.forename: Amanda
authors.initials: A
authors.lastname: Iglesias
authors.affiliation: 4 Research Unit, FISIB, IdISPa, and.
authors.forename: Angel
authors.initials: A
authors.lastname: Rios
authors.affiliation: 4 Research Unit, FISIB, IdISPa, and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jahn
authors.affiliation: 4 Research Unit, FISIB, IdISPa, and.|5 Department of Respiratory Medicine, Hospital Son Espases, Ciber de Enfermedades Respiratorias (CIBERES), Mallorca, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Sauleda
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine and.|2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Miguel
authors.initials: M
authors.lastname: Divo
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine and.|2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Victor
authors.initials: V
authors.lastname: Pinto-Plata
authors.affiliation: 8 Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Lynette
authors.initials: L
authors.lastname: Sholl
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine and.|2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Ivan O
authors.initials: IO
authors.lastname: Rosas
authors.affiliation: 5 Department of Respiratory Medicine, Hospital Son Espases, Ciber de Enfermedades Respiratorias (CIBERES), Mallorca, Spain.|9 Thorax Institute, Hospital Clinic, IDIBAPS, University of Barcelona, and CIBERES, FISIB, Mallorca, Spain.
authors.forename: Alvar
authors.initials: A
authors.lastname: Agustí
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine and.|2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Bartolome R
authors.initials: BR
authors.lastname: Celli
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine and.|2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Owen
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000368:Aged; D017209:Apoptosis; D053264:B-Cell Activating Factor / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects / Q000276:immunology
chemical_list: D053264:B-Cell Activating Factor; D015415:Biomarkers; C505719:TNFSF13B protein, human
keywords: B cell–activating factor of tumor necrosis factor family; autoimmunity; chronic obstructive pulmonary disease; cigarette smoke; lymphoid follicles