title: IFN-λ is able to augment TLR-mediated activation and subsequent function of primary human B cells.
abstract: During the past decade, increased emphasis has been placed on finding alternatives to IFN-α-based therapies. One such alternative, IFN-λ, has shown therapeutic promise in a variety of diseases, but research of this family of cytokines has been primarily focused on their antiviral activities. The goal of the present study was to investigate the role of IFN-λ in the regulation and modulation of B cell function. We show that, similar to IFN-α, IFN-λ1 is able to augment TLR-mediated B cell activation, partially attributed to an upregulation of TLR7 expression, and that both naïve and memory B cells express the limiting type III IFN receptor component, IFN-λR1. Furthermore, this IFN-λ-enhanced B cell activation resulted in increased cytokine and Ig production during TLR7 challenge, most prominently after the addition of helper T cell signals. Ultimately, these elevated cytokine and Ig levels could be partially attributed to the increase in proliferation of TLR7-challenged B cells by both type I and type III IFNs. These findings demonstrate the ability of IFN-λ to boost humoral immunity, an important attribute to consider for further studies on immunity to pathogens, vaccine development, and ongoing advancement of therapeutic strategies aimed at replacing IFN-α-based treatments with IFN-λ.
authors.affiliation: *Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands; and Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rik A
authors.initials: RA
authors.lastname: de Groen
authors.affiliation: *Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands; and Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Zwier M A
authors.initials: ZM
authors.lastname: Groothuismink
authors.affiliation: *Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands; and Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Bi-Sheng
authors.initials: BS
authors.lastname: Liu
authors.affiliation: *Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands; and Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands p.a.boonstra@erasmusmc.nl.
authors.forename: André
authors.initials: A
authors.lastname: Boonstra
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007118:Immunoassay; D007372:Interferons; D007378:Interleukins / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D017471:Receptors, Interferon / Q000096:biosynthesis / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology; D059467:Transcriptome; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; D017471:Receptors, Interferon; D051199:Toll-Like Receptor 7; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C495348:TLR7 protein, human
keywords: IL-29; immunoglobulins; innate immunity; interferon