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产生抗恒河猴(D)的人类淋巴母细胞克隆的衰老

Senescence of a human lymphoblastoid clone producing anti-Rhesus(D).

作者信息

Melamed M D, Gordon J, Ley S J, Edgar D, Hughes-Jones N C

出版信息

Eur J Immunol. 1985 Jul;15(7):742-6. doi: 10.1002/eji.1830150720.

DOI:10.1002/eji.1830150720
PMID:3924635
Abstract

The exploitation of Epstein-Barr virus transformation to generate human lymphoblastoid clones (LCL) producing antibody of predefined specificity has proved highly inefficient. Observations reported here on a cloned LCL producing anti-Rhesus(D) may provide an explanation for the low success rate. Over a few months this clone manifested a progressive loss of capacity to maintain growth in culture. Evidence consistent with terminal differentiation to a cell with the properties of a nonproliferating plasma cell was obtained. These late cells differed from those in the earlier actively cycling phase in that they were no longer able to respond to autostimulatory growth factors although they continued to produce them. This irreversible senescence leading to the death of the clone may be a common feature of virally transformed B cells and this would explain many of the difficulties encountered on this route to the production of human monoclonal antibodies.

摘要

利用爱泼斯坦-巴尔病毒转化来生成产生预定特异性抗体的人淋巴母细胞样克隆(LCL)已被证明效率极低。此处报道的关于一个产生抗恒河猴(D)抗体的克隆LCL的观察结果可能为低成功率提供一个解释。在几个月的时间里,这个克隆表现出在培养中维持生长能力的逐渐丧失。获得了与终末分化为具有非增殖性浆细胞特性的细胞相一致的证据。这些后期细胞与早期活跃循环阶段的细胞不同,因为它们虽然继续产生自刺激生长因子,但不再能够对其作出反应。这种导致克隆死亡的不可逆衰老可能是病毒转化的B细胞的一个共同特征,这将解释在这条生产人单克隆抗体的途径中遇到的许多困难。

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引用本文的文献

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Virology. 1999 May 25;258(1):189-200. doi: 10.1006/viro.1999.9701.
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Human monoclonal antibodies against a plethora of viral pathogens from single combinatorial libraries.源自单个组合文库的针对多种病毒病原体的人源单克隆抗体。
Proc Natl Acad Sci U S A. 1993 May 1;90(9):4141-5. doi: 10.1073/pnas.90.9.4141.
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Elution of antispectrin antibodies from red cells in homozygous beta-thalassaemia.
纯合子β地中海贫血红细胞中抗血影蛋白抗体的洗脱
Clin Exp Immunol. 1986 Mar;63(3):680-6.
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Autocrine growth of human B lymphocytes: maintained response to autostimulatory factors is the special feature of immortalization by Epstein-Barr virus--a hypothesis.人B淋巴细胞的自分泌生长:对自身刺激因子的持续反应是爱泼斯坦-巴尔病毒永生化的特殊特征——一种假说。
Med Oncol Tumor Pharmacother. 1986;3(3-4):269-73. doi: 10.1007/BF02935004.
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Production of human monoclonal IgG and IgM antibodies with anti-D (rhesus) specificity using heterohybridomas.利用异种杂交瘤生产具有抗-D(恒河猴)特异性的人单克隆IgG和IgM抗体。
Immunology. 1986 May;58(1):157-60.
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Immunology. 1985 Oct;56(2):329-35.
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Expression of a human monoclonal anti-(rhesus D) Fab fragment in Escherichia coli with the use of bacteriophage lambda vectors.利用噬菌体λ载体在大肠杆菌中表达人源抗(恒河猴D)Fab片段。
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