{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T02:47:13Z","timestamp":1771037233248,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Gift of Life Donor Program"},{"DOI":"10.13039\/100015537","name":"Department of Pathology and Laboratory Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017830","name":"Penn Center for Precision Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017830","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Solid organ transplant recipients (SOTRs) suffer increased morbidity and mortality due, in part, to chronic immunosuppression. The determination of an individual's immune competence is currently difficult but would improve risk assessment and inform medical decisions. We reasoned that correlating qualitative and quantitative measures of the B-cell compartment with serologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination would reveal novel B-cell\u2013based predictors of immune competence.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed an integrated analysis of B-cell phenotypes, serology, and antibody repertoires in heart, lung, liver, kidney, and multiorgan transplant recipients and healthcare worker (HCW) controls (62 individuals total). We utilized K-means clustering and correlation analyses to identify B-cell features that correlated with vaccine serology.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>K-means clustering identified 3 distinct B-cell compartment\u2013based groups in SOTRs, which correlated with serum responses to SARS-CoV-2 vaccination. Group 1 SOTRs had a naive-dominant circulating B-cell pool and serologic responses closest to HCWs. Group 2 SOTRs had reduced naive but hyperexpanded memory B cells (MBCs) and variable vaccine responses that segregated by immunosuppression. Group 3 SOTRs had lymphopenia across B-cell subsets and poor serologic responses. Antibody repertoire analysis showed reduced clonal diversity across SOTRs, regardless of MBC numbers. Even in SOTRs with the largest immune responses, vaccine-specific B cells showed evidence of reduced maturation and clonal diversity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings reveal a hierarchy of B-cell impairment in SOTRs that can be measured rapidly, with implications for immune monitoring and intervention in immunocompromised individuals.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf250","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T10:47:45Z","timestamp":1748947665000},"page":"e466-e475","source":"Crossref","is-referenced-by-count":3,"title":["B-Cell Subset Representation Predicts SARS-CoV-2 Vaccine Response in Solid Organ Transplant Recipients"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3523-0661","authenticated-orcid":false,"given":"James J","family":"Knox","sequence":"first","affiliation":[{"name":"Department of Pathology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily A","family":"Blumberg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron M","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Department of Pathology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhao","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Kearns","sequence":"additional","affiliation":[{"name":"Department of Pathology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3572-0078","authenticated-orcid":false,"given":"Una","family":"O\u2019Doherty","sequence":"additional","affiliation":[{"name":"Department of Pathology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]},{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine , Atlanta, Georgia ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham","family":"Shaked","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim M","family":"Olthoff","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9478-9211","authenticated-orcid":false,"given":"Eline T","family":"Luning Prak","sequence":"additional","affiliation":[{"name":"Department of Pathology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"2025092306163707800_jiaf250-B1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/nrneph.2014.122","article-title":"Immunization after kidney transplantation\u2014what is necessary and what is safe?","volume":"10","author":"Kotton","year":"2014","journal-title":"Nat Rev Nephrol"},{"key":"2025092306163707800_jiaf250-B2","doi-asserted-by":"crossref","first-page":"ofad369","DOI":"10.1093\/ofid\/ofad369","article-title":"Delayed and attenuated antibody responses to coronavirus disease 2019 vaccination with poor cross-variant neutralization in solid-organ transplant recipients\u2014a prospective longitudinal study","volume":"10","author":"Liew","year":"2023","journal-title":"Open Forum Infect Dis"},{"key":"2025092306163707800_jiaf250-B3","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1084\/jem.124.3.331","article-title":"Disquisitions of original antigenic sin. 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Evidence in man","volume":"124","author":"Fazekas de St Groth","year":"1966","journal-title":"J Exp Med"},{"key":"2025092306163707800_jiaf250-B4","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1126\/science.aag1322","article-title":"Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting","volume":"354","author":"Gostic","year":"2016","journal-title":"Science"},{"key":"2025092306163707800_jiaf250-B5","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1111\/ajt.16503","article-title":"Natural influenza infection produces a greater diversity of humoral responses than vaccination in immunosuppressed transplant recipients","volume":"21","author":"Hirzel","year":"2021","journal-title":"Am J Transplant"},{"key":"2025092306163707800_jiaf250-B6","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/cyto.b.20594","article-title":"Circulating lymphocyte subsets in normal adults are variable and can be clustered into 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