{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T21:10:38Z","timestamp":1774559438450,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Several potent and broadly neutralizing Abs to HIV-1 have been isolated recently from peripheral blood B cells of infected individuals, based on prescreening of Ab activity in the serum. However, little is known regarding the cells that make the Abs that circulate in the blood. Accordingly, we investigated the most likely source, the bone marrow, of chronically HIV-1\u2013infected individuals who were not receiving antiretroviral therapy. Increased frequencies of plasma cells, as well as B cell precursors, namely preB-I and preB-II, and decreased frequencies of mature B cells were observed in bone marrow aspirates of these individuals compared with HIV-negative counterparts. Increased frequencies of bone marrow plasma cells are consistent with known hallmarks of HIV-1 infection, namely hypergammaglobulinemia and increased frequencies of peripheral blood plasmablasts. Levels of HIV-1 envelope (Env)-binding and HIV-1\u2013neutralizing Abs were measured in serum, and corresponding frequencies of Ab-secreting or Env-binding cells were measured in the blood (plasmablasts and memory B cells) and in the bone marrow (plasma cells). A strong correlation was observed between serum HIV-1\u2013specific Abs and Env-specific bone marrow\u2013derived plasma cells, but not circulating plasmablasts or memory B cells. These findings demonstrate that, despite HIV-1\u2013induced phenotypic and functional B cell dysregulation in the peripheral blood and secondary lymphoid tissues, bone marrow plasma cells remain a primary source for circulating HIV-1\u2013specific Abs in HIV-1\u2013infected individuals.<\/jats:p>","DOI":"10.4049\/jimmunol.1402424","type":"journal-article","created":{"date-parts":[[2015,2,14]],"date-time":"2015-02-14T03:27:12Z","timestamp":1423884432000},"page":"2561-2568","source":"Crossref","is-referenced-by-count":16,"title":["Bone Marrow Plasma Cells Are a Primary Source of Serum HIV-1\u2013Specific Antibodies in Chronically Infected Individuals"],"prefix":"10.1093","volume":"194","author":[{"given":"Jairo M","family":"Montezuma-Rusca","sequence":"first","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Moir","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lela","family":"Kardava","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarisa M","family":"Buckner","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Louie","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo J Y","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian H","family":"Santich","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia R","family":"Fankuchen","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Diaz","sequence":"additional","affiliation":[{"name":"Clinical Research Directorate\/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research , Frederick, Maryland 21702"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine R","family":"Daub","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio D","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Center, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae-Wook","family":"Chun","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxing","family":"Li","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"},{"name":"International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute , La Jolla, CA 92037"},{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul C","family":"Braylan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Center, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine R","family":"Calvo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Center, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony S","family":"Fauci","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,3,15]]},"reference":[{"key":"2025030705243589700_r1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1056\/NEJMp1313771","article-title":"Ending AIDS\u2014is an HIV vaccine necessary?","volume":"370","author":"Fauci","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"2025030705243589700_r2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1126\/science.1178746","article-title":"Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target","volume":"326","author":"Walker","year":"2009","journal-title":"Science"},{"key":"2025030705243589700_r3","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1126\/science.1207227","article-title":"Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding","volume":"333","author":"Scheid","year":"2011","journal-title":"Science"},{"key":"2025030705243589700_r4","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nature10373","article-title":"Broad neutralization coverage of HIV by multiple highly potent antibodies","volume":"477","author":"Walker","year":"2011","journal-title":"Nature"},{"key":"2025030705243589700_r5","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1126\/science.1187659","article-title":"Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1","volume":"329","author":"Wu","year":"2010","journal-title":"Science"},{"key":"2025030705243589700_r6","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/nature11544","article-title":"Broad and potent neutralization of HIV-1 by a gp41-specific human antibody","volume":"491","author":"Huang","year":"2012","journal-title":"Nature"},{"key":"2025030705243589700_r7","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1038\/nsmb.2194","article-title":"Prospects for an HIV vaccine: leading B cells down the right path","volume":"18","author":"Moir","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2025030705243589700_r8","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/imr.12075","article-title":"HIV-1 neutralizing antibodies: understanding nature\u2019s pathways","volume":"254","author":"Mascola","year":"2013","journal-title":"Immunol. Rev."},{"key":"2025030705243589700_r9","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.1128\/JVI.07163-11","article-title":"Two distinct broadly neutralizing antibody specificities of different clonal lineages in a single HIV-1-infected donor: implications for vaccine design","volume":"86","author":"Bonsignori","year":"2012","journal-title":"J. Virol."},{"key":"2025030705243589700_r10","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1126\/science.1233989","article-title":"Delineating antibody recognition in polyclonal sera from patterns of HIV-1 isolate neutralization","volume":"340","author":"Georgiev","year":"2013","journal-title":"Science"},{"key":"2025030705243589700_r11","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/nature07930","article-title":"Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals","volume":"458","author":"Scheid","year":"2009","journal-title":"Nature"},{"key":"2025030705243589700_r12","doi-asserted-by":"crossref","first-page":"3952","DOI":"10.1073\/pnas.0813392106","article-title":"Discordant memory B cell and circulating anti-Env antibody responses in HIV-1 infection","volume":"106","author":"Guan","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030705243589700_r13","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0065-2776(08)00405-7","article-title":"Human B cell subsets","volume":"98","author":"Jackson","year":"2008","journal-title":"Adv. Immunol."},{"key":"2025030705243589700_r14","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fimmu.2012.00078","article-title":"Origin and function of circulating plasmablasts during acute viral infections","volume":"3","author":"Fink","year":"2012","journal-title":"Front. Immunol."},{"key":"2025030705243589700_r15","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.it.2011.09.001","article-title":"Staying alive: regulation of plasma cell survival","volume":"32","author":"Tangye","year":"2011","journal-title":"Trends Immunol."},{"key":"2025030705243589700_r16","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/imr.12011","article-title":"The establishment of the plasma cell survival niche in the bone marrow","volume":"251","author":"Chu","year":"2013","journal-title":"Immunol. Rev."},{"key":"2025030705243589700_r17","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1084\/jem.20110363","article-title":"Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated","volume":"208","author":"Liao","year":"2011","journal-title":"J. Exp. Med."},{"key":"2025030705243589700_r18","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.4049\/jimmunol.1103169","article-title":"Homing and adhesion patterns determine the cellular composition of the bone marrow plasma cell niche","volume":"188","author":"Belnoue","year":"2012","journal-title":"J. Immunol."},{"key":"2025030705243589700_r19","doi-asserted-by":"crossref","first-page":"5800","DOI":"10.1128\/JVI.00094-13","article-title":"Characterization of plasmablasts in the blood of HIV-infected viremic individuals: evidence for nonspecific immune activation","volume":"87","author":"Buckner","year":"2013","journal-title":"J. Virol."},{"key":"2025030705243589700_r20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/cyto.b.20429","article-title":"Normalization of bone marrow aspirates for hemodilution in flow cytometric analyses","volume":"76","author":"Loken","year":"2009","journal-title":"Cytometry B Clin. Cytom."},{"key":"2025030705243589700_r21","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1084\/jem.20072683","article-title":"Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals","volume":"205","author":"Moir","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025030705243589700_r22","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.1172\/JCI74351","article-title":"Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals","volume":"124","author":"Kardava","year":"2014","journal-title":"J. Clin. Invest."},{"key":"2025030705243589700_r23","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1128\/JVI.01992-08","article-title":"Analysis of neutralization specificities in polyclonal sera derived from human immunodeficiency virus type 1-infected individuals","volume":"83","author":"Li","year":"2009","journal-title":"J. Virol."},{"key":"2025030705243589700_r24","doi-asserted-by":"crossref","DOI":"10.1002\/0471142735.im1213s100","article-title":"Evaluation of B cell function in patients with HIV","volume-title":"Curr. Protoc. Immunol.","author":"Buckner","year":"2013"},{"key":"2025030705243589700_r25","doi-asserted-by":"crossref","first-page":"13232","DOI":"10.1128\/JVI.78.23.13232-13252.2004","article-title":"Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies","volume":"78","author":"Binley","year":"2004","journal-title":"J. Virol."},{"key":"2025030705243589700_r26","first-page":"S47","article-title":"Human peripheral blood B-cell compartments: a crossroad in B-cell traffic","volume":"78","author":"Perez-Andres","year":"2010","journal-title":"Cytometry B Clin. Cytom."},{"key":"2025030705243589700_r27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cyto.b.20008","article-title":"Immunophenotypic differentiation patterns of normal hematopoiesis in human bone marrow: reference patterns for age-related changes and disease-induced shifts","volume":"60","author":"van Lochem","year":"2004","journal-title":"Cytometry B Clin. Cytom."},{"key":"2025030705243589700_r28","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/cytob.21176","article-title":"The immunophenotypes of blast cells in B-cell precursor acute lymphoblastic leukemia: how different are they from their normal counterparts?","volume":"86","author":"Sedek","year":"2014","journal-title":"Cytometry B Clin. Cytom."},{"key":"2025030705243589700_r29","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/cei.12149","article-title":"Transitional B cell subsets in human bone marrow","volume":"174","author":"Agrawal","year":"2013","journal-title":"Clin. Exp. Immunol."},{"key":"2025030705243589700_r30","doi-asserted-by":"crossref","first-page":"10134","DOI":"10.1073\/pnas.88.22.10134","article-title":"A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals","volume":"88","author":"Burton","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030705243589700_r31","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.4049\/jimmunol.1302783","article-title":"Tissue distribution and dependence of responsiveness of human antigen-specific memory B cells","volume":"192","author":"Giesecke","year":"2014","journal-title":"J. Immunol."},{"key":"2025030705243589700_r32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jim.2008.11.012","article-title":"A method for identification of HIV gp140 binding memory B cells in human blood","volume":"343","author":"Scheid","year":"2009","journal-title":"J. Immunol. Methods"},{"key":"2025030705243589700_r33","doi-asserted-by":"crossref","first-page":"142ra196","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":"2025030705243589700_r34","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.cell.2014.01.052","article-title":"Structural insights on the role of antibodies in HIV-1 vaccine and therapy","volume":"156","author":"West","year":"2014","journal-title":"Cell"},{"key":"2025030705243589700_r35","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.immuni.2012.08.012","article-title":"Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies","volume":"37","author":"Kwong","year":"2012","journal-title":"Immunity"},{"key":"2025030705243589700_r36","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1126\/science.1225416","article-title":"Broadly neutralizing antibodies present new prospects to counter highly antigenically diverse viruses","volume":"337","author":"Burton","year":"2012","journal-title":"Science"},{"key":"2025030705243589700_r37","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S1074-7613(00)80541-5","article-title":"Humoral immunity due to long-lived plasma cells","volume":"8","author":"Slifka","year":"1998","journal-title":"Immunity"},{"key":"2025030705243589700_r38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/40540","article-title":"Lifetime of plasma cells in the bone marrow","volume":"388","author":"Manz","year":"1997","journal-title":"Nature"},{"key":"2025030705243589700_r39","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.1172\/JCI64314","article-title":"Expansion of HIV-specific T follicular helper cells in chronic HIV infection","volume":"122","author":"Lindqvist","year":"2012","journal-title":"J. Clin. Invest."},{"key":"2025030705243589700_r40","doi-asserted-by":"crossref","first-page":"e2013033","DOI":"10.4084\/mjhid.2013.033","article-title":"Bone marrow abnormalities in HIV disease","volume":"5","author":"Dhurve","year":"2013","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"2025030705243589700_r41","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1053\/hupa.2001.22749","article-title":"Detection and characterization of human herpesvirus-8-infected cells in bone marrow biopsies of human immunodeficiency virus-positive patients","volume":"32","author":"Meggetto","year":"2001","journal-title":"Hum. Pathol."},{"key":"2025030705243589700_r42","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1086\/508351","article-title":"HIV-associated monoclonal gammopathy: a retrospective analysis of 25 patients","volume":"43","author":"Amara","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"2025030705243589700_r43","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1084\/jem.20032236","article-title":"Decreased survival of B cells of HIV-viremic patients mediated by altered expression of receptors of the TNF superfamily","volume":"200","author":"Moir","year":"2004","journal-title":"J. Exp. Med."},{"key":"2025030705243589700_r44","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1084\/jem.188.2.233","article-title":"HIV-1 antigen-specific and -nonspecific B cell responses are sensitive to combination antiretroviral therapy","volume":"188","author":"Morris","year":"1998","journal-title":"J. Exp. Med."},{"key":"2025030705243589700_r45","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1086\/526789","article-title":"Normalization of B cell counts and subpopulations after antiretroviral therapy in chronic HIV disease","volume":"197","author":"Moir","year":"2008","journal-title":"J. Infect. Dis."},{"key":"2025030705243589700_r46","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1073\/pnas.0511094103","article-title":"Appearance of immature\/transitional B cells in HIV-infected individuals with advanced disease: correlation with increased IL-7","volume":"103","author":"Malaspina","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030705243589700_r47","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1097\/QAD.0b013e328361a427","article-title":"Impairment of B-cell functions during HIV-1 infection","volume":"27","author":"Amu","year":"2013","journal-title":"AIDS"},{"key":"2025030705243589700_r48","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/imr.12067","article-title":"Insights into B cells and HIV-specific B-cell responses in HIV-infected individuals","volume":"254","author":"Moir","year":"2013","journal-title":"Immunol. Rev."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/194\/6\/2561\/62236690\/1402424.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/194\/6\/2561\/62236690\/1402424.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T06:43:51Z","timestamp":1741329831000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/194\/6\/2561\/7960828"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3]]},"references-count":48,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,3,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1402424","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,3]]},"published":{"date-parts":[[2015,3]]}}}