PT - JOURNAL ARTICLE AU - Nimitha R. Mathew AU - Jayalal K. Jayanthan AU - Ilya Smirnov AU - Jonathan L. Robinson AU - Hannes Axelsson AU - Sravya S. Nakka AU - Aikaterini Emmanouilidi AU - Paulo Czarnewski AU - William T. Yewdell AU - Cristina Lebrero-Fernández AU - Valentina Bernasconi AU - Ali M. Harandi AU - Nils Lycke AU - Nicholas Borcherding AU - Jonathan W. Yewdell AU - Victor Greiff AU - Mats Bemark AU - Davide Angeletti TI - Single cell BCR and transcriptome analysis after respiratory virus infection reveals spatiotemporal dynamics of antigen-specific B cell responses AID - 10.1101/2020.08.24.264069 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.08.24.264069 4099 - http://biorxiv.org/content/early/2020/08/24/2020.08.24.264069.short 4100 - http://biorxiv.org/content/early/2020/08/24/2020.08.24.264069.full AB - B cell responses are a critical component of anti-viral immunity. However, a comprehensive picture of antigen-specific B cell responses, differentiation, clonal proliferation and dynamics in different organs after infection is lacking. Here, we combined single-cell RNA sequencing with single-cell B cell receptor (BCR) characterization of antigen-specific cells in the draining lymph nodes, spleen and lungs after influenza infection. We identify several novel B cell subpopulations forming after infection and find organ-specific differences that persist over the course of the response. We discover important transcriptional differences between memory cells in lungs and lymphoid organs and describe organ-restricted clonal expansion. Strikingly, by combining BCR mutational analysis, monoclonal antibody expression and affinity measurements we find no differences between germinal center (GC)-derived memory and plasmacells, at odds with an affinity-based selection model. By linking antigen-recognition with transcriptional programming, clonal-proliferation and differentiation, these finding provide important advances in our understanding of antiviral B cell immunity.Competing Interest StatementThe authors have declared no competing interest.