{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:30:39Z","timestamp":1792161039709,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sj\u00f6gren's disease (SjD) is a chronic autoimmune disorder characterized by increased circulating self\u2010reactive B cells. While many of these self\u2010reactive B\u00a0cells emerge from the bone marrow, it is not known whether they are excluded from or enriched in specific developmental stages in the periphery. The aim of this study was to determine the immunophenotype of circulating self\u2010reactive B cells in SjD to inform more precise therapeutic targeting. Five major B cell populations: transitional, mature na\u00efve, switched memory, double negative and plasmablasts were single\u2010cell sorted and cultured to produce IgG. Self\u2010reactive IgG was identified by ELISA, flow cytometry of permeabilized HEK293 cells and HEp\u20102 indirect immunofluorescence. Immunoglobulin heavy chains were sequenced by Sanger and next\u2010generation sequencing. Compared with healthy donor controls (HCs), SjD patients had higher frequencies of na\u00efve and CD21<jats:sup>low<\/jats:sup> atypical memory B cell subsets, while antigen\u2010experienced B\u00a0cells expressed more Ki67 and CD86. B cells recognizing intracellular self\u2010antigens were identified in all stages of peripheral B cell development for SjD and HCs, but frequencies of autoreactive B cells were up to 10\u2010fold higher in SjD. Self\u2010reactive transitional B cells expressed higher surface CD38 and lower surface IgM. An increase in self\u2010reactive B cells throughout peripheral development in SjD compared with HCs suggests that counterselection of autoantibody\u2010bearing B cells during central and peripheral tolerance checkpoints are reduced in SjD. Therapeutic strategies focused on depleting B\u00a0cells based on B cell receptor specificity rather than the developmental stage would be more efficient to target self\u2010reactive B cells in SjD.<\/jats:p>","DOI":"10.1111\/imcb.70005","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T09:43:08Z","timestamp":1739785388000},"page":"401-410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Self\u2010reactive B cells are increased in all major stages of peripheral development in Sj\u00f6gren's disease"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5179-4803","authenticated-orcid":false,"given":"Adrian YS","family":"Lee","sequence":"first","affiliation":[{"name":"Centre for Immunology and Allergy Research, Westmead Institute for Medical Research and Faculty of Medicine and Health University of Sydney  Westmead NSW Australia"},{"name":"Department of Immunology Westmead Hospital and Institute of Clinical Pathology and Medical Research, NSW Health Pathology  Westmead NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhankun","family":"Qi","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Allergy Research, Westmead Institute for Medical Research and Faculty of Medicine and Health University of Sydney  Westmead NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine JL","family":"Jackson","sequence":"additional","affiliation":[{"name":"Garvan Institute for Medical Research  Darlinghurst NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7585-7848","authenticated-orcid":false,"given":"Joanne H","family":"Reed","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Allergy Research, Westmead Institute for Medical Research and Faculty of Medicine and Health University of Sydney  Westmead NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.25011"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12766"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2017.01.004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.01.029"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086907"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40215"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.892241"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.065656"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00302"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73111"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-57764-7"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3175"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42683"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2022.2031272"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10445"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12478"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI150985"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.01.009"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.10.6624"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-243071"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.2014.891439"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00321"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39859"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.117"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1115548"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151978"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8648-4_15"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr507"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu138"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt382"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty235"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01686"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv359"}],"container-title":["Immunology &amp; Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imcb.70005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T14:22:04Z","timestamp":1743776524000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imcb.70005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,17]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/imcb.70005"],"URL":"https:\/\/doi.org\/10.1111\/imcb.70005","archive":["Portico"],"relation":{},"ISSN":["0818-9641","1440-1711"],"issn-type":[{"value":"0818-9641","type":"print"},{"value":"1440-1711","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,17]]},"assertion":[{"value":"2025-01-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}