Age-related BCR heavy chain repertoire changes in young and older adults tracked for a decade 9178

Abstract Description Analyzing age-related changes in the B-cell repertoire is critical for understanding declining immune function in the elderly. New naïve B cell are produced in the bone marrow of elderly individuals, but changes in naïve B cell generation with age are poorly characterized. We conducted a longitudinal study of 74 healthy individuals from different age groups,with annual blood sampling for up to 10 years. Immunoglobulin heavy chain libraries prepared from peripheral blood B cells were characterized by high throughput DNA sequencing. We observed a non-linear age-associated decline in the percentage of naive B cells with major changes between 60 and 100 y.o. Younger individuals show more public naive B cell clones compared to the elderly, as well as more similar V gene usage patterns, suggesting increasing divergence of naïve BCR generation among elderly. Over time, V-gene usage in non-naive B-cell repertoires also diverged, particularly in IgG and IgM, potentially driven by the expansion of B-cell clones. Expanded B-cell clones detected longitudinally include those continuing to expand in successive years and showing increasing somatic hypermutation (SHM), in contrast to other large clones that persist without increasing SHM. These data highlight features that could contribute to immunological impairment in the elderly, including increased variation in naïve BCR repertoire, and occupancy of the B cell repertoire by large antigen-experienced clones. Funding Sources Supported by NIAID/NIH grants U19AI090019, U19AI057229, R01AI130398, R01AI127877 Topic Categories Computational and Systems Immunology (COMP)