An abnormal inflammatory response to cigarette smoke is a key feature of chronic obstructive pulmonary disease (COPD), the fourth leading cause of death worldwide. Importantly, even after smoking cessation the inflammation persists and the lung function of patients further declines. Lymphoid follicle formation is associated with disease severity, not only in COPD but in several other chronic inflammatory diseases. This suggests that lymphoid follicles play a role in the persistence of inflammation. Unravelling the mechanisms of lymphoid follicle formation can contribute to a new therapeutic strategy that targets lymphoid follicle formation in chronic inflammatory diseases. We hypothesize that an altered crosstalk between memory B-cells and fibroblasts drives the formation of lymphoid follicles. Furthermore, we anticipate that chronic infection with Haemophilus influenzae –which is present in 30% of patients with COPD –further facilitates the development of lymphoid follicles. Finally, we will investigate whether defective mucosal IgA immunity –as seen in patients with COPD –additionally enhances lymphoid follicle formation.