RT Journal Article
SR Electronic
T1 B Cell Activation and Plasma Cell Differentiation Are Promoted by IFN-λ in Systemic Lupus Erythematosus
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP ji2100339
DO 10.4049/jimmunol.2100339
A1 Barnas, Jennifer L.
A1 Albrecht, Jennifer
A1 Meednu, Nida
A1 Alzamareh, Diana F.
A1 Baker, Cameron
A1 McDavid, Andrew
A1 Looney, R. John
A1 Anolik, Jennifer H.
YR 2021
UL http://www.jimmunol.org/content/early/2021/10/27/jimmunol.2100339.abstract
AB A type I IFN transcriptional profile is upregulated in SLE B cells.Human B cells express type I IFN genes in response to IFN-λ (type III IFN).IFN-λ may enhance TLR7-mediated B cell activation and PC differentiation in SLE.Type I IFN is essential for viral clearance but also contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), via aberrant nucleic acid–sensing pathways, leading to autoantibody production. Type III IFN (IFN-λ) is now appreciated to have a nonredundant role in viral infection, but few studies have addressed the effects of IFN-λ on immune cells given the more restricted expression of its receptor primarily to the epithelium. In this study, we demonstrate that B cells display a prominent IFN gene expression profile in patients with lupus. Serum levels of IFN-λ are elevated in SLE and positively correlate with B cell subsets associated with autoimmune plasma cell development, including CD11c+T-bet+CD21− B cells. Although B cell subsets express all IFN receptors, IFNLR1 strongly correlates with the CD11c+CD21− B cell expansion, suggesting that IFN-λ may be an unappreciated driver of the SLE IFN signature and B cell abnormalities. We show that IFN-λ potentiates gene transcription in human B cells typically attributed to type I IFN as well as expansion of T-bet–expressing B cells after BCR and TLR7/8 stimulation. Further, IFN-λ promotes TLR7/8-mediated plasmablast differentiation and increased IgM production. CD11c+ B cells demonstrate IFN-λ hyperresponsive signaling compared with other B cell subsets, suggesting that IFN-λ accelerates plasma cell differentiation through this putative extrafollicular pathway. In summary, our data support type III IFN-λ as a cytokine promoting the Ab-secreting cell pool in human viral and autoimmune disease.