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

Abstract

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.