Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells.

Ali M. Harandi,Victor Greiff,Jayalal K. Jayanthan,Nils Lycke,Aikaterini Emmanouilidi,Nicholas Borcherding,Cristina Lebrero‐Fernández ,И. В. Смирнов ,Hannes Axelsson,Davide Angeletti,Paulo Czarnewski,William Rodin,Jonathan W. Yewdell,Mats Bemark,William T. Yewdell,Sravya Sowdamini Nakka ,Karin Schön,Jonathan L. Robinson,Valentina Bernasconi,Nimitha R. Mathew

doi:10.1016/j.celrep.2021.109286

Abstract

SummaryB cell responses are critical for antiviral immunity. However, a comprehensive picture of antigen-specific B cell differentiation, clonal proliferation, and dynamics in different organs after infection is lacking. Here, by combining single-cell RNA and B cell receptor (BCR) sequencing of antigen-specific cells in lymph nodes, spleen, and lungs after influenza infection in mice, we identify several germinal center (GC) B cell subpopulations and organ-specific differences that persist over the course of the response. We discover transcriptional differences between memory cells in lungs and lymphoid organs and organ-restricted clonal expansion. Remarkably, we find significant clonal overlap between GC-derived memory and plasma cells. By combining BCR-mutational analyses with monoclonal antibody (mAb) expression and affinity measurements, we find that memory B cells are highly diverse and can be selected from both low- and high-affinity precursors. By linking antigen recognition with transcriptional programming, clonal proliferation, and differentiation, these finding provide important advances in our understanding of antiviral immunity.

Highlights

Viral respiratory infections caused by influenza, orthopneumo, or corona-virus are major concerns worldwide
ScRNA-seq of antigen-specific B cells after influenza infection identifies a range of B cell differentiation stages i.n. mouse infection with Influenza A virus (IAV) is a well-established, acute respiratory viral infection model
Total B cells (50% of cells based on live B220+ IgD+/À and 50% of cells based on live B220+ IgDÀ) were sorted from spleen and lungs of two mice (Figure S1B)

Summary

Introduction

Viral respiratory infections caused by influenza-, orthopneumo-, or corona-virus are major concerns worldwide. B-cell-derived antibodies (Abs) are a central feature of adaptive immunity to viruses. Abs can greatly reduce viral pathogenicity in primary infections and can provide complete protection against disease-causing reinfections (Lam and Baumgarth, 2019). Respiratory virus infections can promote circulating blood cells to generate inducible bronchus-associated lymphoid tissues (iBALTs) in the lung parenchyma (Moyron-Quiroz et al, 2004), resulting in the formation of GC-like structures in mouse lungs by 14 days post infection (dpi) with IAV (Denton et al, 2019; Tan et al, 2019)

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Conclusion