The memory B cell response to influenza vaccination is impaired in older persons

Cell Rep. 2022 Nov 8;41(6):111613. doi: 10.1016/j.celrep.2022.111613.


Influenza infection imparts an age-related increase in mortality and morbidity. The most effective countermeasure is vaccination; however, vaccines offer modest protection in older adults. To investigate how aging impacts the memory B cell response, we track hemagglutinin-specific B cells by indexed flow sorting and single-cell RNA sequencing (scRNA-seq) in 20 healthy adults that were administered the trivalent influenza vaccine. We demonstrate age-related skewing in the memory B cell compartment 6 weeks after vaccination, with younger adults developing hemagglutinin-specific memory B cells with an FcRL5+ "atypical" phenotype, showing evidence of somatic hypermutation and positive selection, which happened to a lesser extent in older persons. We use publicly available scRNA-seq from paired human lymph node and blood samples to corroborate that FcRL5+ atypical memory B cells can derive from germinal center (GC) precursors. Together, this study shows that the aged human GC reaction and memory B cell response following vaccination is defective.

Keywords: B cell; CP: Immunology; aging; antibody selection; influenza; memory; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Viral
  • Hemagglutinins
  • Humans
  • Infant
  • Influenza Vaccines*
  • Influenza, Human* / prevention & control
  • Memory B Cells
  • Vaccination


  • Hemagglutinins
  • Antibodies, Viral
  • Influenza Vaccines