Increased IgA Expression in Lung Lymphoid Follicles in Severe Chronic Obstructive Pulmonary Disease

• Published in: American journal of respiratory and critical care medicine Vol. 199; no. 5; pp. 592 - 602
• Main Authors: Ladjemi, Maha Zohra, Martin, Clémence, Lecocq, Marylène, Detry, Bruno, Nana, Frank Aboubakar, Moulin, Charlotte, Weynand, Birgit, Fregimilicka, Chantal, Bouzin, Caroline, Thurion, Pascal, Carlier, François, Serré, Jef, Gayan-Ramirez, Ghislaine, Delos, Monique, Ocak, Sebahat, Burgel, Pierre Régis, Pilette, Charles
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.03.2019
• Subjects: Acute Disease; Animals; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Case-Control Studies; Chronic obstructive pulmonary disease; Cigarettes; Cytokines; Dendritic cells; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Humans; Immunoglobulin A - metabolism; Immunoglobulins; Infections; Interleukin-6 - metabolism; Interleukins - metabolism; Ligands; Lung - immunology; Lung - metabolism; Lung - pathology; Lung cancer; Lung diseases; Lymphocytes; Male; Mice, Inbred C57BL; Middle Aged; Pulmonary Disease, Chronic Obstructive - immunology; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - pathology; Real-Time Polymerase Chain Reaction; Smoking; Smoking - adverse effects; Smoking - metabolism; Smoking - pathology; Surgery; Tertiary Lymphoid Structures - immunology; Tertiary Lymphoid Structures - metabolism; Tertiary Lymphoid Structures - pathology; Tobacco smoke; Belgium; IgA; lymphoid follicles; B lymphocytes; COPD
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.201802-0352OC

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. To characterize LFs for expression of IgA, the main mucosal antibody. 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. 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. 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.