1. Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin
- Author
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Jianfei Hu, Masaru Kanekiyo, John R. Mascola, Barney S. Graham, Chaim A. Schramm, Julie E. Raab, Jeffrey C. Boyington, Julie E. Ledgerwood, Grace L. Chen, Sarah F. Andrews, Michelle C. Crank, Jason Plyler, Adrian B. McDermott, Xuejun Chen, Michael Chambers, Amy Ransier, Daniel C. Douek, Sam Darko, Hadi M. Yassine, Rebecca A. Gillespie, and Emily E. Coates
- Subjects
0301 basic medicine ,Male ,Hemagglutinin Glycoproteins, Influenza Virus ,Antibodies, Viral ,Influenza A Virus, H7N9 Subtype ,Lymphocyte Activation ,Epitope ,Epitopes ,0302 clinical medicine ,Immunology and Allergy ,Memory B cell ,Cells, Cultured ,education.field_of_study ,B-Lymphocytes ,biology ,Vaccination ,Middle Aged ,Phenotype ,Infectious Diseases ,medicine.anatomical_structure ,Influenza Vaccines ,030220 oncology & carcinogenesis ,Female ,Antibody ,Single-Cell Analysis ,influenza ,Tbet ,Adult ,Immunology ,Population ,B-Lymphocyte Subsets ,Hemagglutinin (influenza) ,Receptors, Antigen, B-Cell ,Virus ,H7N9 ,03 medical and health sciences ,Young Adult ,vaccine response ,Influenza, Human ,medicine ,memory B cells ,Humans ,activated B cells ,hemagglutinin ,education ,B cell ,Ig repertoire ,Virology ,030104 developmental biology ,Antibody Formation ,biology.protein ,Immunologic Memory - Abstract
Vaccine-induced memory B cell responses to evolving viruses like influenza A involve activation of pre-existing immunity and generation of new responses. To define the contribution of these two types of responses, we analyzed the response to H7N9 vaccination in H7N9-naive adults. We performed comprehensive comparisons at the single-cell level of the kinetics, Ig repertoire, and activation phenotype of established pre-existing memory B cells recognizing conserved epitopes and the newly generated memory B cells directed toward H7 strain-specific epitopes. The recall response to conserved epitopes on H7 HA involved a transient expansion of memory B cells with little observed adaptation. However, the B cell response to newly encountered epitopes was phenotypically distinct and generated a sustained memory population that evolved and affinity matured months after vaccination. These findings establish clear differences between newly generated and pre-existing memory B cells, highlighting the challenges in achieving long-lasting, broad protection against an ever-evolving virus.
- Published
- 2019