Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Goldfeld AE,Flemington EK,Boussiotis VA,Theodos CM,Titus RG,Strominger JL,Speck SHdoi
10.1073/pnas.89.24.12198keywords:
subject
Has Abstractpub_date
1992-12-15 00:00:00pages
12198-201issue
24eissn
0027-8424issn
1091-6490journal_volume
89pub_type
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