title: Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice.
abstract: Emerging evidence suggests that autoimmune processes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. We observed that BAFF levels were elevated in smokers and mice exposed to cigarette smoke. In mice, BAFF expression was rapidly induced in the lungs following 4 days of cigarette smoke exposure and remained elevated following 8 and 24 weeks of exposure. Alveolar macrophages were the major source of BAFF Blockade of BAFF using a BAFF receptor-Fc (BAFFR-Fc) construct prevented pulmonary ANA and TLT formation when delivered concurrent with cigarette smoke exposure. Under these conditions, no impact on lung inflammation was observed. However, administration of BAFFR-Fc following smoking cessation markedly reduced the number of TLTs and ANA levels and, of note, reduced pulmonary neutrophilia. Altogether, this study shows for the first time a central role of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggests that BAFF blockade following smoking cessation could have beneficial effects on persistent inflammatory processes.In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. Data presented show that BAFF plays a central role in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggest a therapeutic potential for BAFF blockade in limiting autoimmune processes associated with smoking.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Mathieu C
authors.initials: MC
authors.lastname: Morissette
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.|State Key Laboratory of Respiratory Disease, and Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Medical Sciences Graduate Program, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Pamela
authors.initials: P
authors.lastname: Shen
authors.affiliation: Medical Sciences Graduate Program, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Danya
authors.initials: D
authors.lastname: Thayaparan
authors.affiliation: Centre de Recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Canada.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Bérubé
authors.affiliation: Department of Medicine & Center for Heart Lung Innovation, University of British Columbia St. Paul's Hospital, Vancouver, Canada.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.affiliation: Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen University Medical Center Groningen, Groningen, The Netherlands.|Department of Pathology & Medical Biology, University of Groningen University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Corry-Anke
authors.initials: CA
authors.lastname: Brandsma
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York.|Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Hao
authors.affiliation: Centre de Recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Canada.|Department of Molecular Medicine, Laval University, Québec, Canada.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: MedImmune LLC, Gaithersburg, Maryland.
authors.forename: Rachel
authors.initials: R
authors.lastname: Ettinger
authors.affiliation: MedImmune LLC, Gaithersburg, Maryland.
authors.forename: Ronald
authors.initials: R
authors.lastname: Herbst
authors.affiliation: MedImmune LLC, Gaithersburg, Maryland.
authors.forename: Alison A
authors.initials: AA
authors.lastname: Humbles
authors.affiliation: MedImmune LLC, Gaithersburg, Maryland.
authors.forename: Roland
authors.initials: R
authors.lastname: Kolbeck
authors.affiliation: State Key Laboratory of Respiratory Disease, and Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Respiratory Disease, and Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Rongchang
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada stampfli@mcmaster.ca.|Department of Medicine, Firestone Institute of Respiratory Health at St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stämpfli
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism*; D053264:B-Cell Activating Factor / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D000073865:Cigarette Smoking / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D016540:Smoking Cessation; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D000072717:Tertiary Lymphoid Structures / Q000139:chemically induced / Q000276:immunology; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: D000974:Antibodies, Antinuclear; D053264:B-Cell Activating Factor; D007075:Immunoglobulin M; C505719:TNFSF13B protein, human; C505720:Tnfsf13b protein, mouse
keywords: 
  BAFF
  ; 
  COPD
  ; Animal model; autoantibodies; cigarette smoke