{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T19:54:02Z","timestamp":1771012442808,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T00:00:00Z","timestamp":1667692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA68485"],"award-info":[{"award-number":["P30CA68485"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["KL2TR002245"],"award-info":[{"award-number":["KL2TR002245"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR002243"],"award-info":[{"award-number":["UL1 TR002243"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32 HL087738"],"award-info":[{"award-number":["T32 HL087738"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["T32 AR59039"],"award-info":[{"award-number":["T32 AR59039"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK058404"],"award-info":[{"award-number":["DK058404"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK084246"],"award-info":[{"award-number":["R01 DK084246"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01 BX002882"],"award-info":[{"award-number":["I01 BX002882"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytometry Pt A"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autoreactive B cell subsets have been described in a variety of settings, using multiple classification schemes and cell surface markers also found on healthy cells. CD19<jats:sup>+<\/jats:sup>CD21<jats:sup>lo<\/jats:sup>B cells have been identified as an autoreactive\u2010prone subset of B cells, although the downregulation of CD21 has been observed on a variety of B cell subsets in health and disease. This variation has led to confusion regarding the meaning and applicability of the loss or reduction of CD21 in peripheral B cells. To better understand the relationships between commonly used B cell markers and their associated characteristics, we analyzed human B cells from healthy participants using multiparameter flow cytometry and the visualization algorithm, tSNE. This approach revealed significant phenotypic overlap amongst five previously described autoimmune\u2010prone B cell subsets, including CD19<jats:sup>+<\/jats:sup>CD10<jats:sup>\u2212<\/jats:sup>CD27<jats:sup>\u2212<\/jats:sup>CD21<jats:sup>lo<\/jats:sup>B cells. Interestingly, 12 different subpopulations of CD19<jats:sup>+<\/jats:sup>CD21<jats:sup>lo<\/jats:sup>B cells were identified, some of which mapped to previously described autoreactive populations, while others were consistent with healthy B cells. This suggests that CD21 is downregulated in a variety of circumstances involving B cell activation, all of which are present in low numbers even in healthy individuals. These findings describe the utility of unbiased multiparameter analysis using a relatively limited panel of flow cytometry markers to analyze autoreactive\u2010prone and normal activated B cells.<\/jats:p>","DOI":"10.1002\/cyto.a.24699","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T08:43:57Z","timestamp":1666687437000},"page":"283-294","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Multiparameter analysis of human B lymphocytes identifies heterogeneous<scp>CD19<\/scp><sup>+<\/sup><scp>CD21<sup>lo<\/sup><\/scp>subsets"],"prefix":"10.1002","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6584-1578","authenticated-orcid":false,"given":"Erin M.","family":"Wilfong","sequence":"first","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care, Department of Medicine Vanderbilt University Medical Center Nashville Tennessee USA"},{"name":"Division of Rheumatology and Immunology, Department of Medicine Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine N.","family":"Vowell","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care, Department of Medicine Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie J.","family":"Crofford","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Immunology, Department of Medicine Vanderbilt University Medical Center Nashville Tennessee USA"},{"name":"Department of Microbiology, Pathology and Immunology Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0516-654X","authenticated-orcid":false,"given":"Peggy L.","family":"Kendall","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care, Department of Medicine Vanderbilt University Medical Center Nashville Tennessee USA"},{"name":"Department of Microbiology, Pathology and Immunology Vanderbilt University Medical Center Nashville Tennessee USA"},{"name":"Division of Allergy\/Immunology, Department of Medicine Washington University St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2009.11.017"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1995.341"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2012.05.011"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2015.01.017"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-243071"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202104"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.10.004"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080611"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2020.108364"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-021-00745-5"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3533"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.10.6624"},{"issue":"1577","key":"e_1_2_9_14_1","article-title":"In\u2010depth characterization of CD24(high)CD38(high) transitional human B cells reveals different regulatory profiles","volume":"137","author":"Simon Q","year":"2016","journal-title":"J Allergy Clin Immunol"},{"issue":"65","key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1002\/art.38098","article-title":"Classification criteria for systemic sclerosis: an American College of Rheumatology\/European league against rheumatism collaborative initiative","volume":"2013","author":"Hoogen F","year":"2013","journal-title":"Arthritis Rheum"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2015.05.008"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.22799"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2594"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00302"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2008.09.008"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-331462"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI91250"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37828"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2016.3304"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005687"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072683"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901297"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2017.10.013"},{"key":"e_1_2_9_29_1","first-page":"2:eaai8153","article-title":"Low CD21 expression defines a population of recent germinal center graduates primed for plasma cell differentiation","author":"Lau D","year":"2017","journal-title":"Sci Immunol"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12795"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI96798"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701494"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-0748-5"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.13016"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2017.05.008"},{"key":"e_1_2_9_36_1","doi-asserted-by":"crossref","unstructured":"Dart A. Immunotherapy: Bad B cells. Nat Rev Cancer.2018;18:66.","DOI":"10.1038\/nrc.2018.7"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4149"},{"key":"e_1_2_9_38_1","first-page":"8","article-title":"Evidence for B cell exhaustion in chronic graft\u2010versus\u2010host disease","volume":"8","author":"Khoder A","year":"1937","journal-title":"Front Immunol"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99036"}],"container-title":["Cytometry Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cyto.a.24699","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cyto.a.24699","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cyto.a.24699","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T14:11:56Z","timestamp":1701267116000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cyto.a.24699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,6]]},"references-count":38,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/cyto.a.24699"],"URL":"https:\/\/doi.org\/10.1002\/cyto.a.24699","archive":["Portico"],"relation":{},"ISSN":["1552-4922","1552-4930"],"issn-type":[{"value":"1552-4922","type":"print"},{"value":"1552-4930","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,6]]},"assertion":[{"value":"2022-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}