Mathew NR, Jayanthan JK, Smirnov IV, Robinson JL, Axelsson H, Nakka SS, Emmanouilidi A, Czarnewski P, Yewdell WT, Schön K, Lebrero-Fernández C, Bernasconi V, Rodin W, Harandi AM, Lycke N, Borcherding N, Yewdell JW, Greiff V, Bemark M, Angeletti D
Cell Rep 35 (12) 109286 [2021-06-22; online 2021-06-24]
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.