Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin

Immunity. 2019 Aug 20;51(2):398-410.e5. doi: 10.1016/j.immuni.2019.06.024. Epub 2019 Jul 23.

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.

Keywords: H7N9; Ig repertoire; Tbet; activated B cells; hemagglutinin; influenza; memory B cells; vaccine response.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Antibodies, Viral / metabolism
  • Antibody Formation
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Epitopes / immunology
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Immunologic Memory
  • Influenza A Virus, H7N9 Subtype / physiology*
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Phenotype
  • Receptors, Antigen, B-Cell / genetics
  • Single-Cell Analysis
  • Vaccination
  • Young Adult

Substances

  • Antibodies, Viral
  • Epitopes
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Receptors, Antigen, B-Cell