{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T08:41:47Z","timestamp":1775983307160,"version":"3.50.1"},"posted":{"date-parts":[[2025,3,25]]},"group-title":"Immunology","reference-count":23,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  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\n                  <jats:sup>15<\/jats:sup>\n                  -10\n                  <jats:sup>18<\/jats:sup>\n                  distinct members, although an individual will only sample a fraction of that repertoire at a given time point. The mode of generation of the na\u00efve 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.\n                <\/jats:p>","DOI":"10.1101\/2025.03.20.644446","type":"posted-content","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T14:23:18Z","timestamp":1742912598000},"source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal analysis of drift in the circulating human antibody repertoire over four years"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8739-3219","authenticated-orcid":false,"given":"Collin","family":"Joyce","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Scripps Consortium for HIV\/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3843-9380","authenticated-orcid":false,"given":"Benjamin","family":"Nemoz","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Scripps Consortium for HIV\/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raiza","family":"Bastidas","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Scripps Consortium for HIV\/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9535-2866","authenticated-orcid":false,"given":"Bryan","family":"Briney","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Scripps Consortium for HIV\/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Multi-Omics Vaccine Evaluation Consortium, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6711-9864","authenticated-orcid":false,"given":"Dennis R.","family":"Burton","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Scripps Consortium for HIV\/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041200440327000_2025.03.20.644446v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/381751a0"},{"key":"2026041200440327000_2025.03.20.644446v1.2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00531"},{"key":"2026041200440327000_2025.03.20.644446v1.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1312146110"},{"key":"2026041200440327000_2025.03.20.644446v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2016.03.008"},{"key":"2026041200440327000_2025.03.20.644446v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0879-y"},{"key":"2026041200440327000_2025.03.20.644446v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.05.001"},{"key":"2026041200440327000_2025.03.20.644446v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01230-1"},{"key":"2026041200440327000_2025.03.20.644446v1.8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01452"},{"key":"2026041200440327000_2025.03.20.644446v1.9","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.79254"},{"key":"2026041200440327000_2025.03.20.644446v1.10","doi-asserted-by":"crossref","unstructured":"Briney, B. , and Burton, D.R. (2018). Massively scalable genetic analysis of antibody repertoires. BioRxiv, 447813.","DOI":"10.1101\/447813"},{"key":"2026041200440327000_2025.03.20.644446v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/srep23901"},{"key":"2026041200440327000_2025.03.20.644446v1.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2010.04206.x"},{"key":"2026041200440327000_2025.03.20.644446v1.13","first-page":"215","article-title":"Measuring of the dispersion of individuals and analysis of the distributional patterns","volume":"2","year":"1959","journal-title":"Mem. Fac. Sci. Kyushu Univ., Ser. E (Biol"},{"key":"2026041200440327000_2025.03.20.644446v1.14","doi-asserted-by":"publisher","DOI":"10.1086\/282436"},{"key":"2026041200440327000_2025.03.20.644446v1.15","doi-asserted-by":"publisher","DOI":"10.2307\/3235920"},{"key":"2026041200440327000_2025.03.20.644446v1.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401786101"},{"key":"2026041200440327000_2025.03.20.644446v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.07.027"},{"key":"2026041200440327000_2025.03.20.644446v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3609"},{"key":"2026041200440327000_2025.03.20.644446v1.19","unstructured":"Joshi NA , F.J. (2011). Sickle: A sliding-window, adaptive, quality-based trimming tool for FastQ files. https:\/\/github.com\/najoshi\/sickle."},{"key":"2026041200440327000_2025.03.20.644446v1.20","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-1"},{"key":"2026041200440327000_2025.03.20.644446v1.21","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","year":"2011","journal-title":"EMBnet. journal"},{"key":"2026041200440327000_2025.03.20.644446v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0686-2"},{"key":"2026041200440327000_2025.03.20.644446v1.23","doi-asserted-by":"publisher","DOI":"10.21105\/joss.03021"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.03.20.644446","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T07:44:08Z","timestamp":1775979848000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.03.20.644446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,25]]},"references-count":23,"URL":"https:\/\/doi.org\/10.1101\/2025.03.20.644446","relation":{},"subject":[],"published":{"date-parts":[[2025,3,25]]},"subtype":"preprint"}}