Increased IgA Expression in Lung Lymphoid Follicles in Severe COPD.
(2019) American Journal of Respiratory and Critical Care Medicine — Vol. 199, n° 5, p. 592-602 (2019)
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- (en) 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.
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Ladjemi, M. Z., Martin, C., Lecocq, M., Detry, B., Aboubakar Nana, F., Moulin, C., Weynand, B., Fregimilicka, C., Bouzin, C., Thurion, P., Carlier, F., Serré, J., Gayan-Ramirez, G., Delos, M., Ocak, S., Burgel, P. R., & Pilette, C. (2019). Increased IgA Expression in Lung Lymphoid Follicles in Severe COPD. American Journal of Respiratory and Critical Care Medicine, 199(5), 592-602. https://doi.org/10.1164/rccm.201802-0352OC (Original work published 2019)