{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:53:51Z","timestamp":1781110431560,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1992,12,15]]},"abstract":"<jats:p>The human tumor necrosis factor alpha (TNF-alpha) gene encodes a cytokine whose activities have been implicated in many immunopathological processes, including the activation and differentiation of lymphocytes. Originally identified as a monocyte factor, our studies and those of others have demonstrated that B and T lymphocytes produce TNF-alpha when stimulated by a variety of inducers. We report here that TNF-alpha gene transcription is rapidly and highly induced in three independently derived human Burkitt lymphoma cell lines, as well as in freshly isolated human splenic B cells, activated by antibodies to surface immunoglobulin. This burst in TNF-alpha gene transcription is associated with an induction of TNF-alpha bioactivity in the culture supernatants from stimulated splenic B cells. Moreover, induction of TNF-alpha gene transcription by anti-immunoglobulin was blocked by the immunosuppressants cyclosporin A and FK506. These studies demonstrate that TNF-alpha production is an early event in B-cell activation and they establish the efficacy of using immunosuppressants as probes in dissecting transcriptional activation pathways in human B cells.<\/jats:p>","DOI":"10.1073\/pnas.89.24.12198","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:14:57Z","timestamp":1149063297000},"page":"12198-12201","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":35,"title":["Transcription of the tumor necrosis factor alpha gene is rapidly induced by anti-immunoglobulin and blocked by cyclosporin A and FK506 in human B cells."],"prefix":"10.1073","volume":"89","author":[{"given":"A E","family":"Goldfeld","sequence":"first","affiliation":[{"name":"Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E K","family":"Flemington","sequence":"additional","affiliation":[{"name":"Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V A","family":"Boussiotis","sequence":"additional","affiliation":[{"name":"Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C M","family":"Theodos","sequence":"additional","affiliation":[{"name":"Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R G","family":"Titus","sequence":"additional","affiliation":[{"name":"Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J L","family":"Strominger","sequence":"additional","affiliation":[{"name":"Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S H","family":"Speck","sequence":"additional","affiliation":[{"name":"Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1992,12,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.89.24.12198","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:33:05Z","timestamp":1649856785000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.89.24.12198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,12,15]]},"references-count":0,"journal-issue":{"issue":"24","published-print":{"date-parts":[[1992,12,15]]}},"alternative-id":["10.1073\/pnas.89.24.12198"],"URL":"https:\/\/doi.org\/10.1073\/pnas.89.24.12198","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,12,15]]},"assertion":[{"value":"1992-12-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}