{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:06:01Z","timestamp":1791198361753,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Sonderforschungsbereich","award":["(SFB) 421"],"award-info":[{"award-number":["(SFB) 421"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["Do491\/5-3"],"award-info":[{"award-number":["Do491\/5-3"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB 421"],"award-info":[{"award-number":["SFB 421"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>In systemic lupus erythematosus (SLE), the increased generation of memory B cells and plasma cells leads to autoimmune hypergammaglobulinemia and destructive immunoglobulin deposits in the kidneys. We undertook this study to determine the biologic mechanism driving this overactivation of the B cell compartment, which is the central issue in SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used flow cytometry to analyze expression of the T cell\u2013specific inducible costimulator (ICOS) and its ligand (ICOS\u2010L) on B cells obtained from the peripheral blood of SLE patients. We correlated ICOS\u2010L expression with the differentiation status of the B cells using a large panel of surface antigens. In addition, SLE kidneys were analyzed by immunohistology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found an increased expression of ICOS on CD4+ as well as CD8+ T cells in SLE. At the same time, we documented a down\u2010regulation of ICOS\u2010L on a high proportion of peripheral blood memory B cells. Based on in vitro experiments, we inferred that this ICOS\u2010L down\u2010regulation on B cells was a signature of recent interaction with ICOS+ T cells in vivo. In the kidneys of SLE patients, we found clusters of B cells and plasma cells in close contact with ICOS+ T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Detailed analysis of B cells with down\u2010regulated ICOS\u2010L suggests that ICOS is one of the forces driving the formation of memory B cells and plasma cells in SLE. Furthermore, our identification of plasma cells in areas of T cell\u2013B cell interaction in kidneys suggests that components of a T cell\u2013driven B cell activation process may take place in peripheral tissues in SLE.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20519","type":"journal-article","created":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T21:02:14Z","timestamp":1097269334000},"page":"3211-3220","source":"Crossref","is-referenced-by-count":169,"title":["Involvement of inducible costimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus"],"prefix":"10.1002","volume":"50","author":[{"given":"Andreas","family":"Hutloff","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"B\u00fcchner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Baelde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Odendahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annett","family":"Jacobi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"D\u00f6rner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard 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