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

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 GCreaction andmemory B cell response following vaccination is defective.

Automated summary

This study reveals defects in the human germinal center reaction and memory B cell response following influenza vaccination in elderly individuals.