Tumor necrosis factor alpha is an autocrine growth factor for normal human B cells
| العنوان: | Tumor necrosis factor alpha is an autocrine growth factor for normal human B cells |
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| المؤلفون: | Vassiliki A. Boussiotis, Jack L. Strominger, Anne E. Goldfeld, Lee M. Nadler |
| المصدر: | Proceedings of the National Academy of Sciences. 91:7007-7011 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 1994. |
| سنة النشر: | 1994 |
| مصطلحات موضوعية: | Lymphotoxin alpha, Interleukin 2, Transcription, Genetic, T-Lymphocytes, medicine.medical_treatment, Lymphocyte Activation, Antigen, Antigens, CD, Reference Values, Phosphoprotein Phosphatases, medicine, Humans, CD40 Antigens, Growth Substances, Autocrine signalling, Lymphotoxin-alpha, Cells, Cultured, Interleukin 4, B-Lymphocytes, Multidisciplinary, CD40, biology, Tumor Necrosis Factor-alpha, Calcineurin, Molecular biology, Antigens, Differentiation, B-Lymphocyte, Cytokine, Cyclosporine, biology.protein, Calmodulin-Binding Proteins, Tumor necrosis factor alpha, Interleukin-4, Cell Division, Spleen, Research Article, medicine.drug |
| الوصف: | Transcription of the human tumor necrosis factor alpha (TNF-alpha) gene is one of the earliest events that occurs after stimulation of B or T cells via their antigen receptors. Antibody directed at surface immunoglobulin (anti-Ig) on B cells has previously been shown to induce a rapid burst of TNF-alpha gene transcription, which can be blocked by the immunosuppressants cyclosporin A (CsA) and FK506. Here, TNF-alpha gene transcription is shown also to be highly and rapidly induced in human B cells after stimulation via the CD40 and interleukin 4 pathways, which similarly is inhibited by CsA and a panel of CsA or FK506 analogues that block calcineurin phosphatase activity. Endogenous TNF-alpha produced after stimulation was involved in B-cell proliferation since anti-TNF-alpha monoclonal antibody inhibited both anti-Ig- and anti-CD40-induced B-cell proliferative responses. Moreover, addition of TNF-alpha during stimulation resulted in augmentation of B-cell proliferation, which was also inhibited by anti-TNF-alpha monoclonal antibody. Although lymphotoxin alpha (LT-alpha) mRNA is induced by both pathways, it is not blocked by CsA, whereas LT-beta mRNA is constitutively expressed in B cells. Thus, TNF-alpha is a necessary autocrine growth factor for human B cells stimulated via two independent CsA-sensitive pathways and plays a role similar to that of interleukin 2 in T-cell proliferation. The autocrine nature of TNF-alpha in activated B cells implies a potential role for this cytokine in infection-related polyclonal B-cell expansion and in B-cell malignancies. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c06271ae891697e057ffccf53a6e8dae https://doi.org/10.1073/pnas.91.15.7007 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c06271ae891697e057ffccf53a6e8dae |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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