Goldfeld A E, Flemington E K, Boussiotis V A, Theodos C M, Titus R G, Strominger J L, Speck S H
Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12198-201. doi: 10.1073/pnas.89.24.12198.
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.
人类肿瘤坏死因子α（TNF-α）基因编码一种细胞因子，其活性与许多免疫病理过程有关，包括淋巴细胞的激活和分化。最初被鉴定为单核细胞因子，我们和其他人的研究表明，B淋巴细胞和T淋巴细胞在受到多种诱导剂刺激时会产生TNF-α。我们在此报告，在三种独立衍生的人类伯基特淋巴瘤细胞系以及新鲜分离的人类脾脏B细胞中，当受到表面免疫球蛋白抗体激活时，TNF-α基因转录会迅速且高度诱导。TNF-α基因转录的这种爆发与刺激的脾脏B细胞培养上清液中TNF-α生物活性的诱导有关。此外，抗免疫球蛋白对TNF-α基因转录的诱导被免疫抑制剂环孢素A和FK506阻断。这些研究表明，TNF-α的产生是B细胞激活中的早期事件，并且它们确立了使用免疫抑制剂作为剖析人类B细胞转录激活途径的探针的有效性。
