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人、大鼠或小鼠杂交瘤移植到严重联合免疫缺陷病(SCID)小鼠体内后,会分泌高水平的单克隆抗体。

Human, rat or mouse hybridomas secrete high levels of monoclonal antibodies following transplantation into mice with severe combined immunodeficiency disease (SCID).

作者信息

Ware C F, Donato N J, Dorshkind K

出版信息

J Immunol Methods. 1985 Dec 27;85(2):353-61. doi: 10.1016/0022-1759(85)90144-9.

DOI:10.1016/0022-1759(85)90144-9
PMID:4078317
Abstract

Mice with severe combined immunodeficiency disease (SCID) have been investigated for their ability to grow xenogenic hybridomas of mouse, rat and human origin. Two rat X mouse hybridoma lines (187.1.10 and 3B9) and 1 mouse X mouse hybridoma (2D9) grown in pristane-treated SCID mice as ascites tumors showed a 100-200-fold increase in monoclonal antibody levels over the amount produced in vitro with a total yield up to 0.5 g of antibody per animal. A human X human hybridoma, CLL-11-D1, exhibited a 1000-fold increase in human immunoglobulin levels in ascites (1.3 mg/ml) as compared to that obtained in tissue culture. Analyses of the antibody protein in the SCID ascites produced by these hybridomas using protein electrophoresis, SDS polyacrylamide gel electrophoresis and high resolution isoelectric focusing indicated the antibodies were monoclonal and free from any contaminating immunoglobulins. Yields of monoclonal antibodies of over 90% purity could be obtained from the ascites by a single ammonium sulfate precipitation step. This study indicates that SCID mice provide several significant advantages over other in vivo methods for the production of pure monoclonal antibodies of human, rat, or mouse origin.

摘要

对患有严重联合免疫缺陷病(SCID)的小鼠进行了研究,以考察它们培育源自小鼠、大鼠和人类的异种杂交瘤的能力。在经降植烷处理的SCID小鼠体内作为腹水瘤生长的两株大鼠×小鼠杂交瘤细胞系(187.1.10和3B9)以及1株小鼠×小鼠杂交瘤(2D9),其单克隆抗体水平比体外产生的量增加了100 - 200倍,每只动物的总产量高达0.5 g抗体。一株人×人杂交瘤CLL - 11 - D1,其腹水中人免疫球蛋白水平与在组织培养中获得的相比增加了1000倍(1.3 mg/ml)。使用蛋白质电泳、SDS聚丙烯酰胺凝胶电泳和高分辨率等电聚焦对这些杂交瘤在SCID腹水中产生的抗体蛋白进行分析,结果表明这些抗体是单克隆的,且不含任何污染性免疫球蛋白。通过一步硫酸铵沉淀步骤,可从腹水中获得纯度超过90%的单克隆抗体。这项研究表明,与其他体内方法相比,SCID小鼠在生产源自人、大鼠或小鼠的纯单克隆抗体方面具有几个显著优势。

相似文献

1
Human, rat or mouse hybridomas secrete high levels of monoclonal antibodies following transplantation into mice with severe combined immunodeficiency disease (SCID).人、大鼠或小鼠杂交瘤移植到严重联合免疫缺陷病(SCID)小鼠体内后,会分泌高水平的单克隆抗体。
J Immunol Methods. 1985 Dec 27;85(2):353-61. doi: 10.1016/0022-1759(85)90144-9.
2
Use of severe combined immunodeficient (SCID) mice to produce human hybridoma ascites.利用严重联合免疫缺陷(SCID)小鼠制备人杂交瘤腹水。
Hum Antibodies Hybridomas. 1991 Oct;2(4):190-3.
3
Differential effects of immunosuppressants and antibiotics on human monoclonal antibody production in SCID mouse ascites by five heterohybridomas.
Hybridoma. 1998 Feb;17(1):41-5. doi: 10.1089/hyb.1998.17.41.
4
Growth of rat-mouse hybridomas in nude mice and nude rats.大鼠 - 小鼠杂交瘤在裸鼠和裸大鼠体内的生长
J Immunol Methods. 1982 Dec 30;55(3):319-26. doi: 10.1016/0022-1759(82)90091-6.
5
Parameters affecting ascites tumour formation in mice and monoclonal antibody production.影响小鼠腹水肿瘤形成及单克隆抗体制备的参数。
J Immunol Methods. 1984 Jul 6;71(2):265-72. doi: 10.1016/0022-1759(84)90073-5.
6
Production of human monoclonal antibody in mouse ascites.
Hybridoma. 1984 Summer;3(2):195-9. doi: 10.1089/hyb.1984.3.195.
7
High yields of anti-HLA human monoclonal antibodies can be provided by SCID mice.SCID小鼠能够产生高产量的抗人HLA单克隆抗体。
Hum Immunol. 1992 Dec;35(4):256-9. doi: 10.1016/0198-8859(92)90008-b.
8
Growth of rat-mouse hybridoma cells in immunosuppressed hamsters. An easy and effective method to prepare monoclonal antibodies from heterohybridoma cell lines.大鼠-小鼠杂交瘤细胞在免疫抑制仓鼠体内的生长。一种从异种杂交瘤细胞系制备单克隆抗体的简便有效方法。
J Immunol Methods. 1990 Jun 12;130(1):25-31. doi: 10.1016/0022-1759(90)90295-7.
9
[Comparison of the action of pristan and Freund's incomplete adjuvant on the development of ascites in mice--the recipients of hybridoma cells].[普里斯坦与弗氏不完全佐剂对小鼠(杂交瘤细胞受体)腹水形成作用的比较]
Antibiot Khimioter. 1988 Jul;33(7):530-2.
10
Monoclonal antibody production in murine ascites. II. Production characteristics.小鼠腹水中单克隆抗体的产生。II. 生产特性。
Lab Anim Sci. 1999 Feb;49(1):81-6.

引用本文的文献

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Hybridoma technology; advancements, clinical significance, and future aspects.杂交瘤技术;进展、临床意义及未来展望。
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2
Contact sensitization to oxazolone: involvement of both interferon-gamma and interleukin-4 in oxazolone-specific Ig and T-cell responses.对恶唑酮的接触致敏:γ干扰素和白细胞介素-4在恶唑酮特异性免疫球蛋白和T细胞反应中的作用
Immunology. 1993 Feb;78(2):185-92.
3
The production and application of non-rodent monoclonal antibodies in veterinary science.
非啮齿类单克隆抗体在兽医学中的生产与应用。
Vet Immunol Immunopathol. 1989 Nov 30;23(1-2):1-14. doi: 10.1016/0165-2427(89)90105-0.
4
Limited B cell repertoire in severe combined immunodeficient mice engrafted with peripheral blood mononuclear cells derived from immunodeficient or normal humans.移植了来自免疫缺陷或正常人外周血单个核细胞的重症联合免疫缺陷小鼠的B细胞库有限。
J Clin Invest. 1991 Feb;87(2):658-65. doi: 10.1172/JCI115043.
5
SCID mice in the study of human autoimmune diseases.严重联合免疫缺陷小鼠在人类自身免疫性疾病研究中的应用
Springer Semin Immunopathol. 1992;14(2):159-77. doi: 10.1007/BF00195292.
6
In vivo models of human lymphopoiesis and autoimmunity in severe combined immune deficient mice.严重联合免疫缺陷小鼠中人类淋巴细胞生成和自身免疫的体内模型。
J Clin Immunol. 1992 Sep;12(5):311-24. doi: 10.1007/BF00920788.