B-cell activating factor: The architect of lymphoid follicles in severe COPD

Abstract

Background: The adaptive immune response contributes to the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). One manifestation of adaptive immunity in COPD is the presence of pulmonary lymphoid follicles (LFs) containing B-cells. Aims: B-cell activating factor of TNF family (BAFF) regulates B-cell function in health. Increases in BAFF levels promote autoimmune responses, but BAFF9s role in COPD pathogenesis is unclear. Our goal was to fill this knowledge gap. Methods: 150 subjects were studied: COPD patients (GOLD stages I–IV], healthy smokers (SC) and non-smokers (NSC). We quantified and correlated LF number and size with the number of BAFF-positive and apoptotic B-cells in LFs in COPD vs. control lungs. We tested whether: 1) cigarette smoke extract (CSE) induces B-cell apoptosis which is attenuated by treating cells with recombinant BAFF (rBAFF); and 2) rBAFF inhibits CSE-induced B-cell apoptosis by regulating the NF-κB pathway. Results: GOLD stage IV COPD patients had increased numbers and larger pulmonary LFs than GOLD stages I-II COPD patients and SC. We identified two main types of LFs: 1) type A , predominant in GOLD stage I-II COPD and SC lungs, containing abundant A poptotic but few BAFF-positive cells; and 2) type B , mainly in GOLD stage IV COPD lungs, bigger in size than Type A, and containing abundant B AFF-positive cells but few apoptotic cells. rBAFF blocked CSE-induced B-cell apoptosis by inhibiting CS-induced NF-κB activation. Conclusion: We associate BAFF with the formation and expansion of pulmonary LFs in the severe stages of COPD. Thus, we implicate BAFF in a self-perpetuating loop that may contribute to COPD progression by promoting lung B-cell survival and LF expansion.