@article {Ladjemi980, author = {Maha Zohra Ladjemi and Maryl{\`e}ne Lecocq and Birgit Weynand and Holly Bowen and Hannah J. Gould and Jacques Van Snick and Bruno Detry and Charles Pilette}, title = {Increased IgA production by B-cells in COPD via lung epithelial interleukin-6 and TACI pathways}, volume = {45}, number = {4}, pages = {980--993}, year = {2015}, doi = {10.1183/09031936.00063914}, publisher = {European Respiratory Society}, abstract = {Despite their relevance to mucosal defense, production of IgA and the function of lung B-cells remain unknown in chronic obstructive pulmonary disease (COPD).We assessed IgA synthesis in the lungs of COPD (n=28) and control (n=21) patients, and regulation of B-cells co-cultured with in vitro-reconstituted airway epithelium.In COPD lung tissue, synthesis of IgA1 was increased, which led to its accumulation in subepithelial areas. In vitro, the COPD bronchial epithelium imprinted normal human B-cells for increased production of IgA (mainly IgA1) and maturation into CD38+ plasma cells. These effects were associated with upregulation of TACI (transmembrane activator and CAML interactor) and were observed under resting conditions, while being partly inhibited upon stimulation with cigarette smoke extract. Interleukin (IL)-6 and BAFF (B-cell activating factor)/APRIL (a proliferation-inducing ligand) were upregulated in the COPD epithelium and lung tissue, respectively; the IgA-promoting effect of the COPD bronchial epithelium was inhibited by targeting IL-6 and, to a lower extent, by blocking TACI.These data show that in COPD, the bronchial epithelium imprints B-cells with signals promoting maturation into IgA-producing plasma cells through the action of two epithelial/B-cell axes, namely the IL-6/IL-6 receptor and BAFF-APRIL/TACI pathways, while cigarette smoke partly counteracts this IgA-promoting effect.COPD epithelium induces B-cell maturation of IgA-producing plasma cells via IL-6/IL-6R and BAFF-APRIL/TACI pathways http://ow.ly/D7bR3}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/45/4/980}, eprint = {https://erj.ersjournals.com/content/45/4/980.full.pdf}, journal = {European Respiratory Journal} }