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

作者：Nimitha R. Mathew, Jayalal K. Jayanthan, И. В. Смирнов, Jonathan L. Robinson, Hannes Axelsson, Sravya Sowdamini 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 · 发表于：Cell Reports · 年份：2021 · DOI：10.1016/j.celrep.2021.109286 · 被引用次数：128 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Single-cell and spatial transcriptomics

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.