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

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


    Cell Rep


    . 2021 Jun 22;35(12):109286.
    doi: 10.1016/j.celrep.2021.109286.
    Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells


    Nimitha R Mathew 1 , Jayalal K Jayanthan 1 , Ilya V Smirnov 1 , Jonathan L Robinson 2 , Hannes Axelsson 1 , Sravya S Nakka 1 , Aikaterini Emmanouilidi 1 , Paulo Czarnewski 3 , William T Yewdell 4 , Karin Schön 1 , Cristina Lebrero-Fernández 1 , Valentina Bernasconi 1 , William Rodin 1 , Ali M Harandi 5 , Nils Lycke 1 , Nicholas Borcherding 6 , Jonathan W Yewdell 7 , Victor Greiff 8 , Mats Bemark 9 , Davide Angeletti 10



    Affiliations

    Abstract

    B 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.

    Keywords: B cells; antibodies; antiviral immunity; germinal center; influenza; memory B cells; single-cell BCRseq; single-cell RNA-seq.

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