TY - JOUR T1 - Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - 4857 AU - Gerrit John-Schuster AU - Katrin Hager AU - Thomas Conlon AU - Martin Irmler AU - Johannes Beckers AU - Oliver Eickelberg AU - Ali Önder Yildirim Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/4857.abstract N2 - Chronic obstructive pulmonary disease (COPD) is characterized by a progressive decline in lung function, mainly caused by exposure to cigarette smoke (CS).In the lungs, CS induces an abnormal inflammatory response and leads to the accumulation of B cells organized in iBALT structures. It remains unclear how these structures contribute to CS-induced emphysema and COPD development.In order to identify B cell-dependent mechanisms that drive emphysema development, WT and B cell-deficient (µMT) mice were exposed to CS for 1, 4, or 6 months. Lung function was analyzed and air space enlargement was assessed by stereological analysis of lung tissue. Lung tissue was used for histology and qPCR.Our analyses demonstrate that µMT mice were significantly protected against CS-induced emphysema. In WT compared to µMT mice, chronic CS exposure led to increased lung compliance (0.056±0.001 vs. 0.052±0.001 ml/cmH2O; p<0.005) and mean linear chord length (33.84±2.25 vs. 24.57±3.23 µm; p<0.005) as early as after 4 months of CS exposure. Airspace enlargement was associated with an increased formation of iBALT, which largely consisted of B and T cells. Increased accumulation of macrophages around iBALT and in emphysematous alveolar areas in CS-exposed WT mice was observed and coincided with upregulated MMP12 expression (29-fold vs. controls/2-fold vs. µMT). Blocking B cell-derived IL-10 in vitro revealed a significant reduction of MMP12 expression in macrophages.Our data highlight that B cell-dependent iBALT formation after CS exposure contributes to COPD pathogenesis via IL-10-induced macrophage activation and MMP12 upregulation and provide a new target for therapeutic intervention in COPD patients. ER -