Longitudinal analysis of drift in the circulating human antibody repertoire over four years
Year: 2026
Type: article
Abstract: ABSTRACT The human immune system is a sophisticated network of cells and molecules that plays a vital role in safeguarding the body against a broad range of foreign agents. One of the key components of the immune system is the circulating antibody repertoire, a vast collection of different antibodies that recognize and eliminate foreign agents specifically. The diversity and specificity of the circulating antibody repertoire are essential for effective immunity. In a study of ten healthy donors, we previously demonstrated the accessible human antibody repertoire to be on the order of 10 15 -10 18 distinct members, although an individual will only sample a fraction of that repertoire at a given time point. The mode of generation of the naïve antibody repertoire through random recombination before antigen contact suggests that the composition of the circulating antibody repertoire may drift over time, but the magnitude of this drift is poorly understood. Here, we used high-throughput sequencing to analyze two donors from our original study, approximately four years later. Our results reveal conservation of the size, overall diversity, and gross features of the circulating antibody repertoire, such as V- and J-gene usage and CDRH3 length distribution, over time but suggest substantial changes to fine features of the repertoire, such as combinations of V, J, D gene segments and P and N sequences, which may influence primary responses to newly encountered pathogens as well as to immunization procedures.
Source: Scientific Reports
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: G4668745430, Center for Viral Systems Biology (CViSB), San Diego Center for AIDS Research (SD CFAR), The Multi-omics Vaccine Evaluation (MOVE) Consortium, Consortium for HIV/AIDS Vaccine Development, Genetic, structural and functional profiling of the human antibody response to arenavirus infection
OpenAlex ID: W4408828092
