RT Journal Article
SR Electronic
T1 Transcriptional program of memory B cell activation, broadly binding anti-influenza antibodies, and bystander activation after vaccination revealed by single-cell transcriptomics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 709337
DO 10.1101/709337
A1 Felix Horns
A1 Cornelia L. Dekker
A1 Stephen R. Quake
YR 2019
UL http://biorxiv.org/content/early/2019/07/22/709337.abstract
AB Antibody memory protects humans from many diseases. Protective antibody memory responses require activation of transcriptional programs, cell proliferation, and production of antigen-specific antibodies, but how these aspects of the response are coordinated is poorly understood. We profiled the molecular and cellular features of the antibody response to influenza vaccination by integrating single-cell transcriptomics, longitudinal antibody repertoire sequencing, and antibody binding measurements. Single-cell transcriptional profiling revealed a program of memory B cell activation characterized by CD11c and T-bet expression associated with clonal expansion and differentiation toward effector function. Vaccination elicited an antibody clone which rapidly acquired broad high-affinity hemagglutinin binding during affinity maturation. Unexpectedly, many antibody clones elicited by vaccination do not bind vaccine, demonstrating non-specific activation of bystander antibodies by influenza vaccination. These results offer insight into how molecular recognition, transcriptional programs, and clonal proliferation are coordinated in the human B cell repertoire during memory recall.