Mathew, Nimitha RoseJayanthan, JayalalSmirnov, IlyaRobinson, Jonathan LAxelsson, HannesSowdamini Nakka, SravyaEmmanouilidi, AikateriniCzarnewski, PauloYewdell, William TSchön, KarinLebrero-Fernandez, CristinaBernasconi, ValentinaRodin, WilliamHarandi, Ali MLycke, Nils YBorcherding, NicholasYewdell, Jonathan WGreiff, VictorBemark, MatsAngeletti, Davide2022-06-212022-06-212022Cell reports, 35 (12), 109286https://hdl.handle.net/2077/72256B 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.engText