Interleukin-10 expressing regulatory B cells are decreased in blood of smokers and COPD patients

Abstract

<b>Background:</b> A subset of B cells that negatively regulates immune responses has been termed regulatory B cells (Breg), which can be characterized by IL-10 production. Breg cells are decreased and/or impaired in several inflammatory conditions. <b>Objectives:</b> We determined IL-10 positive (IL-10+) Breg cell percentages in blood of Chronic Obstructive Pulmonary Disease (COPD) patients. <b>Methods:</b> Peripheral blood mononuclear cells (PBMCs) were isolated from never smokers, smokers without airflow limitation and patients with COPD. The percentage of IL-10+ Breg cells in PBMCs and cigarette-smoke extract (CSE) exposed magnetically sorted (MACS) B cells was determined by flowcytometry within the total B cell population and within specific B cell subsets. In addition, protein levels of IL-10 in cell culture supernatant were determined by ELISA. <b>Results:</b> We observed a significantly lower percentage of IL-10+ Breg cells within memory B cells from smokers and patients with COPD, compared to never smokers. IL-10 protein levels were reduced in culture supernatant of smokers and COPD patients and correlated significantly with the total percentage of IL-10+ Breg cells. Furthermore, the addition of CSE significantly reduced the percentage and fluorescent intensity of IL-10+ B cells in a concentration-dependent manner. <b>Conclusion:</b> We demonstrate decreased numbers of IL10+ memory Breg cells in blood of smokers and COPD patients <i>ex vivo</i>, and decreased percentages and impaired Breg function, upon CSE exposure <i>in vitro</i>. Further research is needed to elucidate whether Breg cell numbers are decreased and/or impaired in lung tissue of smokers or COPD patients <i>in vivo</i> and whether this contributes to COPD pathogenesis.