Interferon-λ Enhances the Differentiation of Naive B Cells into Plasmablasts via the mTORC1 Pathway
Mohammedyaseen Syedbasha,
Ferdinando Bonfiglio,
Janina Linnik,
Claudia Stuehler,
Daniel Wüthrich,
Adrian Egli
Affiliations
Mohammedyaseen Syedbasha
Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland; Corresponding author
Ferdinando Bonfiglio
Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland; Swiss Institute for Bioinformatics, Basel, Switzerland
Janina Linnik
Swiss Institute for Bioinformatics, Basel, Switzerland; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland
Claudia Stuehler
Infection Biology Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland
Daniel Wüthrich
Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland; Swiss Institute for Bioinformatics, Basel, Switzerland; Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland
Adrian Egli
Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland; Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland; Corresponding author
Summary: Type III interferon (interferon lambda [IFN-λ]) is known to be a potential immune modulator, but the mechanisms behind its immune-modulatory functions and its impact on plasmablast differentiation in humans remain unknown. Human B cells and their subtypes directly respond to IFN-λ. Using B cell transcriptome profiling, we investigate the immune-modulatory role of IFN-λ in B cells. We find that IFN-λ-induced gene expression in B cells is steady, prolonged, and importantly, cell type specific. Furthermore, IFN-λ enhances the mTORC1 (mammalian/mechanistic target of rapamycin complex 1) pathway in B cells activated by the B cell receptor (BCR/anti-IgM). Engagement of mTORC1 by BCR and IFN-λ induces cell-cycle progress in B cells. Subsequently, IFN-λ boosts the differentiation of naive B cells into plasmablasts upon activation, and the cells gain effector functions such as cytokine release (IL-6 and IL-10) and antibody production. Our study shows how IFN-λ systematically boosts the differentiation of naive B cells into plasmablasts by enhancing the mTORC1 pathway and cell-cycle progression in activated B cells.
