Airway epithelial cells produce B cell-activating factor of TNF family by an IFN-beta-dependent mechanism.
Activation of B cells in the airways is now believed to be of great importance in immunity to pathogens, and it participates in the pathogenesis of airway diseases. However, little is known about the mechanisms of local activation of B cells in airway mucosa. We investigated the expression of members of the B cell-activating TNF superfamily (B cell-activating factor of TNF family (BAFF) and a proliferation-inducing ligand (APRIL)) in resting and TLR ligand-treated BEAS-2B cells and primary human bronchial epithelial cells (PBEC). In unstimulated cells, expression of BAFF and APRIL was minimal. However, BAFF mRNA was significantly up-regulated by TLR3 ligand (dsRNA), but not by other TLR ligands, in both BEAS-2B cells (376-fold) and PBEC (224-fold). APRIL mRNA was up-regulated by dsRNA in PBEC (7-fold), but not in BEAS-2B cells. Membrane-bound BAFF protein was detectable after stimulation with dsRNA. Soluble BAFF protein was also induced by dsRNA (> 200 pg/ml). The biological activity of the epithelial cell-produced BAFF was verified using a B cell survival assay. BAFF was also strongly induced by IFN-beta, a cytokine induced by dsRNA. Induction of BAFF by dsRNA was dependent upon protein synthesis and IFN-alphabeta receptor-JAK-STAT signaling, as indicated by studies with cycloheximide, the JAK inhibitor I, and small interfering RNA against STAT1 and IFN-alphabeta receptor 2. These results suggest that BAFF is induced by dsRNA in airway epithelial cells and that the response results via an autocrine pathway involving IFN-beta. The production of BAFF and APRIL by epithelial cells may contribute to local accumulation, activation, class switch recombination, and Ig synthesis by B cells in the airways.
Kato
Atsushi
A
Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Truong-Tran
Ai Q
AQ
Scott
Alan L
AL
Matsumoto
Kenji
K
Schleimer
Robert P
RP
D053264:B-Cell Activating Factor / Q000096:biosynthesis*; D001980:Bronchi / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000096:biosynthesis; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D016899:Interferon-beta / Q000502:physiology*; D008024:Ligands; D012330:RNA, Double-Stranded / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000096:biosynthesis; D048069:Tumor Necrosis Factors / Q000096:biosynthesis
D053264:B-Cell Activating Factor; D016207:Cytokines; D005938:Glucocorticoids; D008024:Ligands; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D048069:Tumor Necrosis Factors; D023201:CD40 Ligand; D016899:Interferon-beta