TY - JOUR
T1 - Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells
AU - Mathew, Nimitha R.
AU - Jayanthan, Jayalal K.
AU - Smirnov, Ilya V.
AU - Robinson, Jonathan L.
AU - Axelsson, Hannes
AU - Nakka, Sravya S.
AU - Emmanouilidi, Aikaterini
AU - Czarnewski, Paulo
AU - Yewdell, William T.
AU - Schön, Karin
AU - Lebrero-Fernández, Cristina
AU - Bernasconi, Valentina
AU - Rodin, William
AU - Harandi, Ali M.
AU - Lycke, Nils
AU - Borcherding, Nicholas
AU - Yewdell, Jonathan W.
AU - Greiff, Victor
AU - Bemark, Mats
AU - Angeletti, Davide
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2021/6/22
Y1 - 2021/6/22
N2 - 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.
AB - 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.
KW - B cells
KW - antibodies
KW - antiviral immunity
KW - germinal center
KW - influenza
KW - memory B cells
KW - single-cell BCRseq
KW - single-cell RNA-seq
UR - http://www.scopus.com/inward/record.url?scp=85108282008&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2021.109286
DO - 10.1016/j.celrep.2021.109286
M3 - Article
C2 - 34161770
AN - SCOPUS:85108282008
SN - 2639-1856
VL - 35
JO - Cell Reports
JF - Cell Reports
IS - 12
M1 - 109286
ER -