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

• DOI: 10.1016/j.celrep.2022.111613
• Publication Date: 2022-11-08T16:05:33Z
• Authors: Alice R. Burton; Stephane M. Guill...; William S. Foster; Adam K. Wheatley; Danika L. Hill; Edward J. Carr; Michelle A. Linte...
• Keywords: Aged, 80 and over; 0301 basic medicine; QH301-705.5; FOS: Clinical medicine; Vaccination; Immunology; Correction; Infant; Infectious Disease; Cell Biology; Antibodies, Viral; Article; 3. Good health; 03 medical and health sciences; Hemagglutinins; 0302 clinical medicine; Memory B Cells; Influenza Vaccines; Influenza, Human; Humans; Biology (General); Aged

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.