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. 1992 Dec 15;89(24):12198–12201. doi: 10.1073/pnas.89.24.12198

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.

A E Goldfeld 1, E K Flemington 1, V A Boussiotis 1, C M Theodos 1, R G Titus 1, J L Strominger 1, S H Speck 1
PMCID: PMC50726  PMID: 1281550

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.

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