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

Cell reports (2021-06-24)
Nimitha R Mathew, Jayalal K Jayanthan, Ilya V Smirnov, Jonathan L Robinson, Hannes Axelsson, Sravya S Nakka, Aikaterini Emmanouilidi, Paulo Czarnewski, William T Yewdell, Karin Schön, Cristina Lebrero-Fernández, Valentina Bernasconi, William Rodin, Ali M Harandi, Nils Lycke, Nicholas Borcherding, Jonathan W Yewdell, Victor Greiff, Mats Bemark, Davide Angeletti
RÉSUMÉ

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.

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HiTrap® Protein G High Performance, Cytiva 17-0404-03, pack of 2 × 1 mL