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白细胞介素-6对小鼠杂交瘤细胞系具有抗增殖作用,并能提高其抗体产生能力。

Interleukin-6 is antiproliferative to a mouse hybridoma cell line and promotive for its antibody productivity.

作者信息

Makishima F, Terada S, Mikami T, Suzuki E

机构信息

Institute for Genetics, University of Cologne, Germany.

出版信息

Cytotechnology. 1992;10(1):15-23. doi: 10.1007/BF00376096.

DOI:10.1007/BF00376096
PMID:1369102
Abstract

Monoclonal antibody production by hybridoma cells at moderately slowed growth states would be favorable for commercial scale production since cells can devote their resources to performing the differentiated function, immunoglobulin production. We found that a purified recombinant human interleukin-6, which had been reported to support or stimulate proliferation of B cell hybridoma/plasmacytoma cells, suppressed growth of a hybridoma cell line in serum-free medium. In the presence of the interleukin, the growth-suppressed cells were viable for remarkably long periods in batch culture, and after removal of the interleukin from the culture medium, they started to proliferate at their normal growth rate. As the concentration of the interleukin increased in the culture, the growth rate decreased and the specific antibody productivity (antibody production rate per cell) increased to 5-fold of control at 10 U ml-1 (2 ng ml-1) of the interleukin.

摘要

杂交瘤细胞在生长适度减缓状态下产生单克隆抗体有利于商业化规模生产,因为细胞能够将资源用于执行分化功能,即免疫球蛋白的产生。我们发现,一种纯化的重组人白细胞介素-6,据报道它能支持或刺激B细胞杂交瘤/浆细胞瘤细胞的增殖,但在无血清培养基中却抑制了一种杂交瘤细胞系的生长。在白细胞介素存在的情况下,生长受抑制的细胞在分批培养中能存活很长时间,并且从培养基中去除白细胞介素后,它们开始以正常生长速率增殖。随着培养基中白细胞介素浓度的增加,生长速率降低,而特异性抗体生产率(每细胞的抗体产生速率)在白细胞介素浓度为10 U/ml(2 ng/ml)时增加到对照的5倍。

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1
Interleukin-6 is antiproliferative to a mouse hybridoma cell line and promotive for its antibody productivity.白细胞介素-6对小鼠杂交瘤细胞系具有抗增殖作用,并能提高其抗体产生能力。
Cytotechnology. 1992;10(1):15-23. doi: 10.1007/BF00376096.
2
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J Biotechnol. 1994 May 15;34(2):175-83. doi: 10.1016/0168-1656(94)90087-6.

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本文引用的文献

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A kinetic analysis of hybridoma growth and metabolism in batch and continuous suspension culture: effect of nutrient concentration, dilution rate, and pH.分批和连续悬浮培养中杂交瘤生长与代谢的动力学分析:营养物浓度、稀释率和pH值的影响
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A macrophage-derived factor required by plasmacytomas for survival and proliferation in vitro.浆细胞瘤在体外生存和增殖所需的一种巨噬细胞衍生因子。
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Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors.
来自沙鼠-小鼠T细胞杂交瘤的条件培养基可改善抗体分泌。
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Establishing apoptosis resistant cell lines for improving protein productivity of cell culture.建立抗凋亡细胞系以提高细胞培养的蛋白质产率。
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Co-expression of bcl-2 and bag-1, apoptosis suppressing genes, prolonged viable culture period of hybridoma and enhanced antibody production.bcl-2 和 bag-1 基因的共表达,凋亡抑制基因,延长杂交瘤的存活培养期,并增强抗体的产生。
Cytotechnology. 1999 Sep;31(1-2):143-51. doi: 10.1023/A:1008080407581.
7
Sericin, a protein derived from silkworms, accelerates the proliferation of several mammalian cell lines including a hybridoma.丝胶,一种来源于家蚕的蛋白质,能加速几种包括杂交瘤细胞在内的哺乳动物细胞系的增殖。
Cytotechnology. 2002 Nov;40(1-3):3-12. doi: 10.1023/A:1023993400608.
8
Growth control of hybridoma cells with an artificially induced EpoR-gp130 heterodimer.用人工诱导的 EpoR-gp130 异二聚体控制杂交瘤细胞的生长。
Cytotechnology. 2006 Nov;52(3):171-9. doi: 10.1007/s10616-006-9035-2. Epub 2006 Dec 5.
9
Enhanced antibody production of human-human hybridomas by retinoic acid.维甲酸增强人-人杂交瘤的抗体产生。
Cytotechnology. 2000 Jul;33(1-3):83-8. doi: 10.1023/A:1008155609072.
10
Anti-apoptotic genes, bag-1 and bcl-2, enabled hybridoma cells to survive under treatment for arresting cell cycle.抗凋亡基因bag-1和bcl-2使杂交瘤细胞在细胞周期阻滞处理下得以存活。
Cytotechnology. 1997;25(1-3):17-23. doi: 10.1023/a:1007954103572.
白细胞介素6增强多能造血祖细胞依赖白细胞介素3的增殖。
Proc Natl Acad Sci U S A. 1987 Dec;84(24):9035-9. doi: 10.1073/pnas.84.24.9035.
4
B-cell-stimulatory factor 2 (beta 2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells.B细胞刺激因子2(β2干扰素)作为成熟小鼠T细胞产生白细胞介素2的第二信号发挥作用。
Proc Natl Acad Sci U S A. 1987 Nov;84(21):7629-33. doi: 10.1073/pnas.84.21.7629.
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Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor.鉴定人26-kD蛋白,即干扰素β2(IFN-β2),为白细胞介素1和肿瘤坏死因子诱导产生的一种B细胞杂交瘤/浆细胞瘤生长因子。
J Exp Med. 1987 Mar 1;165(3):914-9. doi: 10.1084/jem.165.3.914.
6
Interleukin-HP1, a T cell-derived hybridoma growth factor that supports the in vitro growth of murine plasmacytomas.白细胞介素-HP1,一种由T细胞衍生的杂交瘤生长因子,可支持小鼠浆细胞瘤的体外生长。
J Exp Med. 1987 Mar 1;165(3):641-9. doi: 10.1084/jem.165.3.641.
7
Recombinant human B cell stimulatory factor 2 (BSF-2/IFN-beta 2) regulates beta-fibrinogen and albumin mRNA levels in Fao-9 cells.重组人B细胞刺激因子2(BSF-2/干扰素-β2)调节Fao-9细胞中β-纤维蛋白原和白蛋白的mRNA水平。
FEBS Lett. 1987 Aug 31;221(1):18-22. doi: 10.1016/0014-5793(87)80344-7.
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Recombinant human interleukin 6 (B-cell stimulatory factor 2) is a potent inducer of differentiation of mouse myeloid leukemia cells (M1).重组人白细胞介素6(B细胞刺激因子2)是小鼠髓样白血病细胞(M1)分化的有效诱导剂。
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IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells.白细胞介素-6/ B细胞刺激因子-2在体外诱导细胞毒性T细胞过程中作为杀伤辅助因子发挥作用。
J Immunol. 1988 Sep 1;141(5):1543-9.
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Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas.人多发性骨髓瘤中自分泌产生及对BSF-2/IL-6的需求
Nature. 1988 Mar 3;332(6159):83-5. doi: 10.1038/332083a0.