{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:35:36Z","timestamp":1791164136411,"version":"4.1.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"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":[[2009,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This study reports on the characterization of B cells of germinal center (GC)-like structures infiltrating the salivary glands (SGs) of patients with Sj\u00f6gren\u2019s syndrome. Eight two-color combinations were devised to characterize the phenotype of these B cells in 11 SG specimens selected from biopsies obtained from 40 Sj\u00f6gren\u2019s syndrome patients and three normal tonsils. The 9G4 mAb, which recognizes V4.34-encoded autoAbs, enabled us to identify autoreactive B cells. Quantitative RT-PCR was used to determine the level of mRNAs for activation-induced cytidine deaminase (AICDA), repressors and transcription factors. CD20+IgD\u2212CD38+CD21+CD24\u2212 B cells, similar to those identified in tonsil GCs, were seen in the SGs of four patients and, and since they expressed AICDA, they were termed \u201creal GCs\u201d. CD20+IgD+CD38\u2212CD21+CD24+ B cells, seen in aggregates from the remaining seven samples, were characteristically type 2 transitional B cells and marginal zone-type B cells. They lacked AICDA mRNAs and were termed \u201caggregates\u201d. Real GCs from SGs contained mRNAs for Pax-5 and Bcl-6, like tonsil GC cells, whereas aggregates contained mRNAs for Notch-2, Blimp-1, IRF-4, and BR3, similar to marginal zone B cells. Further experimental data in support of this dichotomy included the restriction of CXCR5 expression to real GC cells, while sphingosine 1-phosphate receptor 1 was expressed only in aggregates. In contrast, both types of B cell clusters expressed the idiotype recognized by the 9G4 mAb. Our data indicate that, in SGs, a minority of B cell clusters represent genuine GC cells, while the majority manifest features of being type 2 transitional B cells and marginal zone cells. Interestingly, both types of B cell aggregates include autoreactive B cells.<\/jats:p>","DOI":"10.4049\/jimmunol.0803588","type":"journal-article","created":{"date-parts":[[2009,3,5]],"date-time":"2009-03-05T20:01:20Z","timestamp":1236283280000},"page":"3540-3547","source":"Crossref","is-referenced-by-count":162,"title":["Ectopic Germinal Centers Are Rare in Sj\u00f6gren\u2019s Syndrome Salivary Glands and Do Not Exclude Autoreactive B Cells"],"prefix":"10.1093","volume":"182","author":[{"given":"La\u00ebtitia","family":"Le Pottier","sequence":"first","affiliation":[{"name":"Equipe d'Accueil 2216 and Institut F\u00e9d\u00e9ratif de Recherche 418, Science et Ing\u00e9nierie en Biologie-Sant\u00e9, Universit\u00e9 de Brest, Brest, and Universit\u00e9 Europ\u00e9enne de Bretagne , Brest,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Devauchelle","sequence":"additional","affiliation":[{"name":"Equipe d'Accueil 2216 and Institut F\u00e9d\u00e9ratif de Recherche 418, Science et Ing\u00e9nierie en Biologie-Sant\u00e9, Universit\u00e9 de Brest, Brest, and Universit\u00e9 Europ\u00e9enne de Bretagne , Brest,","place":["France"]},{"name":"Centre Hospitalier Universitaire de Brest , Brest,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Fautrel","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 620, and Institut F\u00e9d\u00e9ratif de Recherche 140 Core Histopathology Platform, Universit\u00e9 de Rennes I, and Universit\u00e9 Europ\u00e9enne de Bretagne , Rennes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Capucine","family":"Daridon","sequence":"additional","affiliation":[{"name":"Equipe d'Accueil 2216 and Institut F\u00e9d\u00e9ratif de Recherche 418, Science et Ing\u00e9nierie en Biologie-Sant\u00e9, Universit\u00e9 de Brest, Brest, and Universit\u00e9 Europ\u00e9enne de Bretagne , Brest,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Saraux","sequence":"additional","affiliation":[{"name":"Equipe d'Accueil 2216 and Institut F\u00e9d\u00e9ratif de Recherche 418, Science et Ing\u00e9nierie en Biologie-Sant\u00e9, Universit\u00e9 de Brest, Brest, and Universit\u00e9 Europ\u00e9enne de Bretagne , Brest,","place":["France"]},{"name":"Centre Hospitalier Universitaire de Brest , Brest,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Youinou","sequence":"additional","affiliation":[{"name":"Equipe d'Accueil 2216 and Institut F\u00e9d\u00e9ratif de Recherche 418, Science et Ing\u00e9nierie en Biologie-Sant\u00e9, Universit\u00e9 de Brest, Brest, and Universit\u00e9 Europ\u00e9enne de Bretagne , Brest,","place":["France"]},{"name":"Centre Hospitalier Universitaire de Brest , Brest,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques-Olivier","family":"Pers","sequence":"additional","affiliation":[{"name":"Equipe d'Accueil 2216 and Institut F\u00e9d\u00e9ratif de Recherche 418, Science et Ing\u00e9nierie en Biologie-Sant\u00e9, Universit\u00e9 de Brest, Brest, and Universit\u00e9 Europ\u00e9enne de Bretagne , Brest,","place":["France"]},{"name":"Centre Hospitalier Universitaire de Brest , Brest,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,3,15]]},"reference":[{"key":"2026012807055071600_R1","first-page":"1301","article-title":"Sj\u00f6gren\u2019s syndrome. 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Immunol.","year":"2008"},{"key":"2026012807055071600_R16","first-page":"2160","article-title":"Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sj\u00f6gren\u2019s syndrome.","volume-title":"Arthritis Rheum.","year":"2002"},{"key":"2026012807055071600_R17","first-page":"713","article-title":"Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone.","volume-title":"Nat. Immunol.","year":"2004"},{"key":"2026012807055071600_R18","first-page":"54","article-title":"Follicular shuttling of marginal zone B cells facilitates antigen transport.","volume-title":"Nat. Immunol.","year":"2008"},{"key":"2026012807055071600_R19","first-page":"589","article-title":"Control of inflammation, cytokine expression, and germinal center formation by BCL-6.","volume-title":"Science","year":"1997"},{"key":"2026012807055071600_R20","first-page":"553","article-title":"Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme.","volume-title":"Cell","year":"2000"},{"key":"2026012807055071600_R21","first-page":"2868","article-title":"Phenotype and genotype of interfollicular large B cells, a subpopulation of lymphocytes often with dendritic morphology.","volume-title":"Blood","year":"2003"},{"key":"2026012807055071600_R22","first-page":"2545","article-title":"A novel human B cell subpopulation representing the initial germinal center population to express AID.","volume-title":"Blood","year":"2007"},{"key":"2026012807055071600_R23","first-page":"7276","article-title":"Regulated expression of BAFF-binding receptors during human B cell differentiation.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012807055071600_R24","first-page":"555","article-title":"Initiation of plasma-cell differentiation is independent of Blimp-1.","volume-title":"Immunity","year":"2007"},{"key":"2026012807055071600_R25","first-page":"348","article-title":"The genetic basis of human Vh4 gene family-associated cross-reactive idiotype expression in CD5+ and CD5\u2212 cord blood B-lymphocyte clones.","volume-title":"Scand. J. Immunol.","year":"1993"},{"key":"2026012807055071600_R26","first-page":"3205","article-title":"Germinal center exclusion of autoreactive B cells is defective in human systemic lupus erythematosus.","volume-title":"J. Clin. Invest.","year":"2005"},{"key":"2026012807055071600_R27","first-page":"377","article-title":"Germinal center checkpoints in B cell tolerance in 3H9 transgenic mice.","volume-title":"Int. Immunol.","year":"2004"},{"key":"2026012807055071600_R28","first-page":"59","article-title":"Association of BAFF\/BLyS overexpression and altered B cell differentiation with Sj\u00f6gren\u2019s syndrome.","volume-title":"J. Clin. Invest.","year":"2002"},{"key":"2026012807055071600_R29","first-page":"19","article-title":"B lymphocytes are required for development and treatment of autoimmune diseases.","volume-title":"Ann. NY Acad. Sci.","year":"2005"},{"key":"2026012807055071600_R30","first-page":"1134","article-title":"Aberrant expression of BAFF by B lymphocytes infiltrating the salivary glands of patients with primary Sj\u00f6gren\u2019s syndrome.","volume-title":"Arthritis Rheum.","year":"2007"},{"key":"2026012807055071600_R31","first-page":"2633","article-title":"Ectopic expression of the B cell-attracting chemokine on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center-like structures in Sj\u00f6gren\u2019s syndrome.","volume-title":"Arthritis Rheum.","year":"2001"},{"key":"2026012807055071600_R32","first-page":"115","article-title":"BAFF-induced changes in BCR-containing lipid rafts in Sj\u00f6gren\u2019s syndrome.","volume-title":"Arthritis Rheum.","year":"2006"},{"key":"2026012807055071600_R33","first-page":"938","article-title":"Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease: the salivary glands of patients with Sj\u00f6gren\u2019s syndrome.","volume-title":"J. 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Rev.","year":"2007"},{"key":"2026012807055071600_R39","first-page":"554","article-title":"Classification criteria for Sj\u00f6gren\u2019s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group.","volume-title":"Ann. Rheum. Dis.","year":"2002"},{"key":"2026012807055071600_R40","first-page":"310","article-title":"Improvement of Sj\u00f6gren\u2019s syndrome after two infusions of rituximab (anti-CD20).","volume-title":"Arthritis Rheum.","year":"2007"},{"key":"2026012807055071600_R41","first-page":"154","article-title":"CD4 cytotoxic and dendritic cells in the immunopathologic lesion of Sj\u00f6gren\u2019s syndrome.","volume-title":"Clin. Exp. Immunol.","year":"1999"},{"key":"2026012807055071600_R42","first-page":"375","article-title":"Measurement of co-localization of objects in dual-color confocal images.","volume-title":"J. 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