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

doi:10.1016/j.celrep.2020.108211

Interferon-λ Enhances the Differentiation of Naive B Cells into Plasmablasts via the mTORC1 Pathway

Cell Rep. 2020 Oct 6;33(1):108211. doi: 10.1016/j.celrep.2020.108211.

Authors

Mohammedyaseen Syedbasha¹, Ferdinando Bonfiglio², Janina Linnik³, Claudia Stuehler⁴, Daniel Wüthrich⁵, Adrian Egli⁶

Affiliations

¹ Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland. Electronic address: [email protected].
² Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland; Swiss Institute for Bioinformatics, Basel, Switzerland.
³ Swiss Institute for Bioinformatics, Basel, Switzerland; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
⁴ Infection Biology Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland.
⁵ 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.
⁶ Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland; Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland. Electronic address: [email protected].

PMID: 33027651
DOI: 10.1016/j.celrep.2020.108211

Abstract

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.

Keywords: B cell activation; JAK-STAT signaling; cell cycle; effector function; immune modulation; interferon lambda; mTORC1 pathway; phosphorylation; plasmablast differentiation; transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B-Lymphocytes / immunology*
Cell Differentiation
Humans
Interferons / immunology*
Mechanistic Target of Rapamycin Complex 1 / genetics*
Plasma Cells / metabolism*

Substances

Interferons
Mechanistic Target of Rapamycin Complex 1