Maha Zohra Ladjemi1,2, Clémence Martin3,4, Marylène Lecocq1,5, Bruno Detry1,2, Frank Aboubakar Nana1, Charlotte Moulin1, Birgit Weynand6, Chantal Fregimilicka7, Caroline Bouzin7, Pascal Thurion8, François Carlier1, Jef Serré9, Ghislaine Gayan-Ramirez9, Monique Delos8, Sebahat Ocak1,10, Pierre Régis Burgel3,4, Charles Pilette1,2,5. 1. 1 Pôle de Pneumologie, ORL & Dermatologie. 2. 2 Institute for Walloon Excellence in Lifesciences and Biotechnology, Brussels, Belgium. 3. 3 Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 4. 4 Service de Pneumologie, Hôpital Cochin, Paris, France. 5. 5 Service de Pneumologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium. 6. 6 Pathologische Ontleedkunde, UZ Leuven, Leuven, Belgium. 7. 7 Institut de Recherche Expérimentale & Clinique Imaging Platform, Institut de Recherche Expérimentale & Clinique, Université Catholique de Louvain, Brussels, Belgium. 8. 8 Service d'anatomopathologie, CHU de Mont-Godinne, Yvoir, Belgium. 9. 9 KU Leuven, Laboratory of Respiratory Diseases, Leuven, Belgium; and. 10. 10 Service de Pneumologie, CHU Université Catholique de Louvain Namur (Site Godinne), Yvoir, Belgium.
Abstract
RATIONALE: Accumulation of B cells and lymphoid follicles (LFs) has been described in chronic obstructive pulmonary disease (COPD) airways, but the functional status of lung B cells remains poorly known. OBJECTIVES: To characterize LFs for expression of IgA, the main mucosal antibody. METHODS: The presence of B cells and LFs, including intrafollicular IgA expression, were determined in the lung from patients with COPD (n = 37) versus control subjects (n = 34) by immunohistochemistry. We also evaluated follicular IgA responses in the lungs from mice infected with Pseudomonas aeruginosa (PAO1) (n = 10 per group) and in smoking mice. MEASUREMENTS AND MAIN RESULTS: Whereas in smokers B-cell numbers slightly increased, robust increases in B-cell and LF numbers (mainly in distal airways) were only observed in severe COPD. Most follicular B cells were IgM+ (70-80%), but IgA+ (and not IgG+) B-cell numbers were increased in LFs from severe COPD compared with control subjects (twofold, 44.7% vs. 25.2%), and this was significant in distal but not proximal airways. Follicular IgA response was also observed in PAO1-infected mouse lungs, but not after smoke exposure. Moreover, follicular IgA expression associated with expression of IL-21, which was very potent to activate immunoglobulin production in vitro. CONCLUSIONS: This study shows that IgA production occurs in peribronchiolar LFs from severe COPD, where IL-21-producing T cells are present, and presumably represents a feature of exacerbated mucosal adaptive immune responses against microbial and/or self-antigens.
RATIONALE: Accumulation of B cells and lymphoid follicles (LFs) has been described in chronic obstructive pulmonary disease (COPD) airways, but the functional status of lung B cells remains poorly known. OBJECTIVES: To characterize LFs for expression of IgA, the main mucosal antibody. METHODS: The presence of B cells and LFs, including intrafollicular IgA expression, were determined in the lung from patients with COPD (n = 37) versus control subjects (n = 34) by immunohistochemistry. We also evaluated follicular IgA responses in the lungs from mice infected with Pseudomonas aeruginosa (PAO1) (n = 10 per group) and in smoking mice. MEASUREMENTS AND MAIN RESULTS: Whereas in smokers B-cell numbers slightly increased, robust increases in B-cell and LF numbers (mainly in distal airways) were only observed in severe COPD. Most follicular B cells were IgM+ (70-80%), but IgA+ (and not IgG+) B-cell numbers were increased in LFs from severe COPD compared with control subjects (twofold, 44.7% vs. 25.2%), and this was significant in distal but not proximal airways. Follicular IgA response was also observed in PAO1-infectedmouse lungs, but not after smoke exposure. Moreover, follicular IgA expression associated with expression of IL-21, which was very potent to activate immunoglobulin production in vitro. CONCLUSIONS: This study shows that IgA production occurs in peribronchiolar LFs from severe COPD, where IL-21-producing T cells are present, and presumably represents a feature of exacerbated mucosal adaptive immune responses against microbial and/or self-antigens.
Entities:
Keywords:
B lymphocytes; COPD; IgA; lymphoid follicles
Authors: Peter Heukels; Jennifer A C van Hulst; Menno van Nimwegen; Carian E Boorsma; Barbro N Melgert; Jan H von der Thusen; Bernt van den Blink; Rogier A S Hoek; Jelle R Miedema; Stefan F H Neys; Odilia B J Corneth; Rudi W Hendriks; Marlies S Wijsenbeek; Mirjam Kool Journal: Respir Res Date: 2019-10-24
Authors: Timothy S Blackwell; Vasiliy V Polosukhin; Bradley W Richmond; Samira Mansouri; Ana Serezani; Sergey Novitskiy; Jessica B Blackburn; Rui-Hong Du; Hubaida Fuseini; Sergey Gutor; Wei Han; Jacob Schaff; Georgii Vasiukov; Matthew K Xin; Dawn C Newcomb; Lei Jin Journal: Mucosal Immunol Date: 2020-09-23 Impact factor: 7.313