{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:41:14Z","timestamp":1765546874030,"version":"3.37.3"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T00:00:00Z","timestamp":1651363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19 AI117891"],"award-info":[{"award-number":["U19 AI117891"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["F30 AI124568"],"award-info":[{"award-number":["F30 AI124568"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The ability of the humoral immune system to generate Abs capable of specifically binding a myriad of Ags is critically dependent on the somatic hypermutation program. This program induces both templated mutations (i.e., gene conversion) and untemplated mutations. In humans, somatic hypermutation is widely believed to result in untemplated point mutations. In this study, we demonstrate detection of large-scale templated events that occur in human memory B cells and circulating plasmablasts. We find that such mutations are templated intrachromosomally from IGHV genes and interchromosomally from IGHV pseudogenes as well as other homologous regions unrelated to IGHV genes. These same donor regions are used in multiple individuals, and they predominantly originate from chromosomes 14, 15, and 16. In addition, we find that exogenous sequences placed at the IgH locus, such as LAIR1, undergo templated mutagenesis and that homology appears to be the major determinant for donor choice. Furthermore, we find that donor tracts originate from areas in proximity with open chromatin, which are transcriptionally active, and are found in spatial proximity with the IgH locus during the germinal center reaction. These donor sequences are inserted into the Ig gene segment in association with overlapping activation-induced cytidine deaminase hotspots. Taken together, these studies suggest that diversity generated during the germinal center response is driven by untemplated point mutations as well as templated mutagenesis using local and distant regions of the genome.<\/jats:p>","DOI":"10.4049\/jimmunol.2100434","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T18:00:51Z","timestamp":1649872851000},"page":"2141-2153","source":"Crossref","is-referenced-by-count":2,"title":["Somatic Diversification of Rearranged Antibody Gene Segments by Intra- and Interchromosomal Templated Mutagenesis"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4995-6017","authenticated-orcid":false,"given":"Gordon A","family":"Dale","sequence":"first","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Center, Emory University , Atlanta, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0398-8715","authenticated-orcid":false,"given":"Daniel J","family":"Wilkins","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Center, Emory University , Atlanta, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5135-9596","authenticated-orcid":false,"given":"Jordan","family":"Rowley","sequence":"additional","affiliation":[{"name":"Department of Biology, Emory University , Atlanta, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7716-8504","authenticated-orcid":false,"given":"Christopher D","family":"Scharer","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine, Emory University , Atlanta, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5049-2571","authenticated-orcid":false,"given":"Christopher M","family":"Tipton","sequence":"additional","affiliation":[{"name":"Lowance Center for Human Immunology, Department of Medicine, Emory University , Atlanta, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Hom","sequence":"additional","affiliation":[{"name":"Lowance Center for Human Immunology, Department of Medicine, Emory University , Atlanta, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2432-1840","authenticated-orcid":false,"given":"Jeremy M","family":"Boss","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine, Emory University , Atlanta, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5140-4337","authenticated-orcid":false,"given":"Victor","family":"Corces","sequence":"additional","affiliation":[{"name":"Department of Biology, Emory University , Atlanta, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"Sanz","sequence":"additional","affiliation":[{"name":"Lowance Center for Human Immunology, Department of Medicine, Emory University , Atlanta, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0247-7016","authenticated-orcid":false,"given":"Joshy","family":"Jacob","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Center, Emory University , Atlanta, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,5,1]]},"reference":[{"key":"2025021009050519100_r1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.cell.2015.10.004","article-title":"Germinal center selection and the antibody response to influenza","volume":"163","author":"Victora","year":"2015","journal-title":"Cell"},{"key":"2025021009050519100_r2","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0092-8674(00)00078-7","article-title":"Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme","volume":"102","author":"Muramatsu","year":"2000","journal-title":"Cell"},{"key":"2025021009050519100_r3","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0960-9822(02)00717-0","article-title":"AID is essential for immunoglobulin V gene conversion in a cultured B cell line","volume":"12","author":"Harris","year":"2002","journal-title":"Curr. 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