{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T20:53:02Z","timestamp":1761511982329},"reference-count":43,"publisher":"American Society for Microbiology","issue":"18","license":[{"start":{"date-parts":[[2004,9,15]],"date-time":"2004-09-15T00:00:00Z","timestamp":1095206400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2004,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>B-cell antigen receptor signaling is initiated upon binding of the antigen to membrane-bound immunoblobulin (Ig), and the anti-Ig antibody (Ab) mimics this signaling. In B cells latently infected with Epstein-Barr virus (EBV), the same signals induce virus activation. We examine here whether rheumatoid factors (RFs), autoantibodies directed against the Fc portion of IgG, induce EBV and B-cell activation. As a source of RFs, RF-producing lymphoblastoid cell line (LCL) clones were isolated from peripheral blood mononuclear cells (PBMC) and synovial cells from patients with rheumatoid arthritis (RA) by EBV transformation. Burkitt's lymphoma-derived Akata cells, which are highly responsive to EBV activation by anti-Ig Abs, were used for the assay of EBV activation. Akata cells expressed IgG3 as membrane-bound Ig. RFs from a synovium-derived LCL were directed to IgG3 and induced EBV activation in 16 to 18% of Akata cells, whereas RFs from another synovium-derived LCL were directed to IgG1 and did not induce EBV activation. Pretreatment of RFs with the purified Fc fragment of human IgG completely abolished EBV activation. Furthermore, B-cell activation was assessed by incorporation of [<jats:sup>3<\/jats:sup>H]thymidine. RFs from synovium-derived LCLs efficiently induced B-cell activation, and the addition of CD40 ligand had a synergistic effect. On the other hand, RFs from PBMC-derived LCLs were polyreactive, had a lower affinity to IgG, and did not induce EBV and B-cell activation. The present findings imply a possible role for RFs as EBV and B-cell activators.<\/jats:p>","DOI":"10.1128\/jvi.78.18.9918-9923.2004","type":"journal-article","created":{"date-parts":[[2004,8,26]],"date-time":"2004-08-26T22:23:27Z","timestamp":1093559007000},"page":"9918-9923","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Rheumatoid Factors Induce Signaling from B Cells, Leading to Epstein-Barr Virus and B-Cell Activation"],"prefix":"10.1128","volume":"78","author":[{"given":"Lixin","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Tumor Virology, Institute for Genetic Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Hakoda","sequence":"additional","affiliation":[{"name":"Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuya","family":"Iwabuchi","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuyoshi","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Hokkaido University Graduate School of Medicine, Sapporo"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takao","family":"Koike","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Hokkaido University Graduate School of Medicine, Sapporo"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoyuki","family":"Kamatani","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenzo","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Tumor Virology, Institute for Genetic Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110127"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/357080a0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.168.6.1979"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1990.tb02929.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01857093"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.2000.00731.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.11.5825"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.6.3752-3758.1995"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"4788","DOI":"10.4049\/jimmunol.144.12.4788","volume":"144","year":"1990","unstructured":"Daibata, M., R. 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