{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T08:55:12Z","timestamp":1792313712418,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,6,3]],"date-time":"2004-06-03T00:00:00Z","timestamp":1086220800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine phenotypic and functional abnormalities of blood B cell subsets in patients with systemic sclerosis (SSc).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cell surface marker expression was determined by flow cytometry. Spontaneous apoptosis was evaluated by annexin V expression with flow cytometric analysis. IgG production by isolated IgD\u2212 memory B cells was examined by enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The numbers of blood CD27\u2212 naive B cells from SSc patients were increased compared with normal control cells, while memory B cells expressing medium levels of CD27 and plasmablasts expressing high levels of CD27 were reduced. In contrast, plasmablasts were the predominant population in patients with systemic lupus erythematosus (SLE). Memory B cells in SSc showed increased expression of activation markers, including CD80, CD86, and CD95, relative to normal controls. Consistent with CD95 up\u2010regulation, SSc memory B cells exhibited augmented spontaneous apoptosis after 24\u2010hour incubation; augmented apoptosis may explain the reduced memory B cell number. Nonetheless, isolated IgD\u2212 SSc memory B cells treated with stimuli had an enhanced ability to produce IgG. Furthermore, expression of CD19, a critical signal transduction molecule of B cells that regulates autoantibody production, was significantly increased in memory B cells as well as in naive B cells in SSc. In contrast, CD19 expression was decreased in SLE B cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SSc patients have distinct abnormalities of blood homeostasis and B cell compartments, characterized by expanded naive B cells and activated but diminished memory B cells. Our results suggest that CD19 overexpression in SSc memory B cells is related to their hyperreactivity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20274","type":"journal-article","created":{"date-parts":[[2004,6,3]],"date-time":"2004-06-03T17:02:27Z","timestamp":1086282147000},"page":"1918-1927","source":"Crossref","is-referenced-by-count":291,"title":["Altered blood B lymphocyte homeostasis in systemic sclerosis: Expanded naive B cells and diminished but activated memory B cells"],"prefix":"10.1002","volume":"50","author":[{"given":"Shinichi","family":"Sato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazukiko","family":"Takehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,6,3]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"202","article-title":"Scleroderma (systemic sclerosis): classification, subsets, and pathogenesis","volume":"15","author":"LeRoy EC","year":"1988","journal-title":"J Rheumatol"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-857X(05)70297-0"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780200410"},{"key":"e_1_2_6_5_2","first-page":"59","article-title":"Polyclonal B lymphocyte activation in progressive systemic sclerosis","volume":"29","author":"Famularo G","year":"1989","journal-title":"J Clin Lab Immunol"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215078"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1998.tb01447.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.9.1679"},{"key":"e_1_2_6_9_2","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.4049\/jimmunol.148.12.3700","article-title":"IgM and IgG but not cytokine secretion is restricted to the CD27+ B lymphocyte subset","volume":"148","author":"Maurer D","year":"1992","journal-title":"J Immunol"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830270835"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(00)01605-4"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI3409"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.9.1691"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.10.5970"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10445"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.4.2361"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10949"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.7.3610"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230510"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780251101"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350606"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6635"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80418-5"},{"key":"e_1_2_6_24_2","doi-asserted-by":"crossref","first-page":"4371","DOI":"10.4049\/jimmunol.157.10.4371","article-title":"CD19 regulates B lymphocyte signaling thresholds critical for the development of B\u20101 lineage cells and autoimmunity","volume":"157","author":"Sato S","year":"1996","journal-title":"J Immunol"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.3109\/08830189909088489"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(91)90121-4"},{"key":"e_1_2_6_27_2","first-page":"375","article-title":"Phenotype of peripheral blood lymphocytes in patients with progressive systemic sclerosis: activated T lymphocytes and the effect of D\u2010penicillamine therapy","volume":"69","author":"Freundlich B","year":"1987","journal-title":"Clin Exp Immunol"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780290606"},{"key":"e_1_2_6_29_2","doi-asserted-by":"crossref","first-page":"4662","DOI":"10.4049\/jimmunol.158.10.4662","article-title":"CD19 expression levels regulate B lymphocyte development: human CD19 restores normal function in mice lacking endogenous CD19","volume":"158","author":"Sato S","year":"1997","journal-title":"J Immunol"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711660307"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/144.3_Pt_1.706"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1081\/IMM-100105067"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1177\/153537020222700907"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5669"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.152.3.1453"},{"key":"e_1_2_6_36_2","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.4049\/jimmunol.155.5.2703","article-title":"T and B cell collaboration is essential for the autoantibody response to DNA topoisomerase I in systemic sclerosis","volume":"155","author":"Kuwana M","year":"1995","journal-title":"J Immunol"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.10.1639"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80045-X"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/40.2.205"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10541"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10467"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.20274","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.20274","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T23:18:21Z","timestamp":1700781501000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.20274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2004,6]]}},"alternative-id":["10.1002\/art.20274"],"URL":"https:\/\/doi.org\/10.1002\/art.20274","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,6]]}}}