{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:45:31Z","timestamp":1790203531304,"version":"4.1.0"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,3,17]]},"abstract":"<jats:p>Despite the rare appearance of potent HIV-neutralizing mAbs in infected individuals requiring prolonged affinity maturation, little is known regarding this process in the majority of viremic individuals. HIV-infected individuals with chronic HIV viremia have elevated numbers of nonconventional tissue-like memory (TLM) B cells that predominate in blood over conventional resting memory (RM) B cells. Accordingly, we investigated affinity maturation in these 2 memory B cell populations. Analysis of IgG-expressing TLM B cells revealed a higher number of cell divisions compared with RM B cells; however, TLM B cells paradoxically displayed significantly lower frequencies of somatic hypermutation (SHM). To assess Ab reactivity in TLM and RM B cells, single-cell cloning was performed on HIV envelope CD4\u2013binding site\u2013sorted (CD4bs-sorted) B cells from 3 individuals with chronic HIV viremia. Several clonal families were present among the 127 cloned recombinant mAbs, with evidence of crosstalk between TLM and RM B cell populations that was largely restricted to non-VH4 families. Despite evidence of common origins, SHM frequencies were significantly decreased in TLM-derived mAbs compared with SHM frequencies in RM-derived mAbs. However, both cell populations had lower frequencies of SHMs than did broadly neutralizing CD4bs\u2013specific mAbs. There was a significant correlation between SHM frequencies and the HIV-neutralizing capacities of the mAbs. Furthermore, HIV neutralization was significantly higher in the RM-derived mAbs compared with that seen in  the TLM-derived mAbs, and both SHM frequencies and neutralizing capacity were lowest in TLM-derived mAbs with high polyreactivity. Thus, deficiencies in memory B cells that arise during chronic HIV viremia provide insight into the inadequacy of the Ab response in viremic individuals.<\/jats:p>","DOI":"10.1172\/jci.insight.84610","type":"journal-article","created":{"date-parts":[[2016,3,16]],"date-time":"2016-03-16T11:00:44Z","timestamp":1458126044000},"source":"Crossref","is-referenced-by-count":43,"title":["Maturational characteristics of HIV-specific antibodies in viremic individuals"],"prefix":"10.1172","volume":"1","author":[{"given":"Eric","family":"Meffre","sequence":"first","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Louie","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Bannock","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo J.Y.","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1074-4241","authenticated-orcid":true,"given":"Jason","family":"Ho","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody C.","family":"Frear","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lela","family":"Kardava","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9374-2374","authenticated-orcid":true,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisa M.","family":"Buckner","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia R.","family":"Fankuchen","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen R.","family":"Gittens","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Wook","family":"Chun","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxing","family":"Li","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, USA."},{"name":"Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony S.","family":"Fauci","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Moir","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2016,3,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000092"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12067"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328361a427"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00094-13"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01844-08"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511094103"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-05-285528"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.9.1679"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.9.1691"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nri3447"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939531"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241146"},{"key":"B13","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2011.00081","article-title":"The relationship between CD27 negative and positive B cell populations in human peripheral blood","volume":"2","author":"Wu","year":"2011","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.6.3728"},{"key":"B15","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2012.00302","article-title":"Advances in human B cell phenotypic profiling","volume":"3","author":"Kaminski","year":"2012","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050879"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072683"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.09.006"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-243071"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-312942"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901297"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901984106"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2013.12.001"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/art.37828"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2013.10.006"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/science.1255904"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3746"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74351"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-345579"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060964"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45685"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nature13300"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20150585"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12462"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035356"},{"issue":"142","key":"B36","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3003752","article-title":"High-resolution definition of vaccine-elicited B cell responses against the HIV primary receptor binding site","volume":"4","author":"Sundling","year":"2012","journal-title":"Sci Transl Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2008.11.012"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2012.08.011"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00734-12"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/nature07930"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12075"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.3.1414-1426.2006"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000445"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nature09385"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.018"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/nature12053"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1126\/science.1207227"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.03.004"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1126\/science.1207532"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075032"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1126\/science.1187659"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.007"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01762-08"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001028"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/nm1624"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121970"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402168"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000912"},{"key":"B59","first-page":"4","article-title":"Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function","author":"Portugal","year":"2015","journal-title":"Elife"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121932"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3109"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.02.010"},{"key":"B63"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1126\/science.3107127"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102022"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/nri3802"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501209"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/nri3862"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2013.10.004"},{"issue":"10","key":"B70","doi-asserted-by":"crossref","first-page":"7972","DOI":"10.1128\/JVI.73.10.7972-7980.1999","article-title":"CD40-Mediated induction of CD4 and CXCR4 on B lymphocytes correlates with restricted susceptibility to human immunodeficiency virus type 1 infection: potential role of B lymphocytes as a viral reservoir","volume":"73","author":"Moir","year":"1999","journal-title":"J Virol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-430959"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086907"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.16.10108-10125.2005"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402424"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/84610\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T14:23:18Z","timestamp":1779200598000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/84610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,17]]},"references-count":74,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2016,3,17]]},"published-print":{"date-parts":[[2016,3,17]]}},"alternative-id":["10.1172\/jci.insight.84610"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.84610","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,17]]},"article-number":"e84610"}}