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一种单克隆抗体抗-6C2的研发,其参与CD4辅助性T细胞与活化B细胞的相互作用。

Development of a monoclonal antibody, anti-6C2, which is involved in the interaction of CD4 T helper cells and activated B cells.

作者信息

Torimoto Y, Sugita K, Weinberg D S, Dang N H, Donahue C, Letvin N L, Schlossman S F, Morimoto C

机构信息

Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.

出版信息

J Immunol. 1991 Apr 1;146(7):2176-84.

PMID:1706389
Abstract

We have developed a mAb anti-6C2, by immunizing mice with T cell line derived from the Callithrix jacchus (common marmoset). Anti-6C2 is reactive with approximately 50% of unfractionated T cells, 50% of CD4+ cells, and 40% of CD8+ cells. Regarding CD4+ cells, anti-6C2-reactive cells substantially overlap with the CD29+CD45RO+ Th cell population. Moreover, anti-6C2 can divide these T cells into 6C2+ and 6C2- subpopulations. The CD4+CD45RO+6C2+ cells maximally respond to soluble Ag such as tetanus toxoid and provide strong helper function for PWM-driven B cell IgG synthesis. Most interestingly, anti-6C2 was also reactive against activated B cells but not resting B cells; furthermore, this epitope was inducible through activation of resting B cells or B cell line. Biochemical characterization showed that anti-6C2 precipitated two glycoproteins with the relative molecular weights of 180,000 and 95,000 from 125I-surface labeled cell lysate. Sequential immunoprecipitation studies demonstrated that these two glycoproteins were the lymphocyte function-associated antigen (LFA-1) Ag complex (CD11a/18). Significantly, although this antibody did not inhibit cytotoxic killer T cell responses and Ag-induced T cell proliferation as did conventional anti-LFA-1, it did inhibit PWM-driven B cell IgG synthesis. Because 6C2 expression was induced after B cell activation, the above results strongly suggest that the 6C2 molecule may play a role in the interaction of CD4 helper cells and activated B lymphocytes.

摘要

我们通过用来自普通狨猴(Callithrix jacchus)的T细胞系免疫小鼠,开发出了一种抗6C2单克隆抗体。抗6C2与约50%的未分级T细胞、50%的CD4⁺细胞和40%的CD8⁺细胞发生反应。对于CD4⁺细胞,抗6C2反应性细胞与CD29⁺CD45RO⁺辅助性T细胞群体有大量重叠。此外,抗6C2可将这些T细胞分为6C2⁺和6C2⁻亚群。CD4⁺CD45RO⁺6C2⁺细胞对破伤风类毒素等可溶性抗原反应最强,并为PWM驱动的B细胞IgG合成提供强大的辅助功能。最有趣的是,抗6C2也与活化的B细胞反应,但不与静止的B细胞反应;此外,该表位可通过静止B细胞或B细胞系的活化诱导产生。生化特性表明,抗6C2从¹²⁵I表面标记的细胞裂解物中沉淀出两种相对分子质量分别为180,000和95,000的糖蛋白。连续免疫沉淀研究表明,这两种糖蛋白是淋巴细胞功能相关抗原(LFA-1)抗原复合物(CD11a/18)。值得注意的是,尽管该抗体不像传统抗LFA-1那样抑制细胞毒性杀伤性T细胞反应和抗原诱导的T细胞增殖,但它确实抑制PWM驱动的B细胞IgG合成。由于B细胞活化后诱导了6C2表达,上述结果强烈表明6C2分子可能在CD4辅助性T细胞与活化的B淋巴细胞相互作用中发挥作用。

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Development of a monoclonal antibody, anti-6C2, which is involved in the interaction of CD4 T helper cells and activated B cells.一种单克隆抗体抗-6C2的研发,其参与CD4辅助性T细胞与活化B细胞的相互作用。
J Immunol. 1991 Apr 1;146(7):2176-84.
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引用本文的文献

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Regulated expression and function of CD11c/CD18 integrin on human B lymphocytes. Relation between attachment to fibrinogen and triggering of proliferation through CD11c/CD18.人B淋巴细胞上CD11c/CD18整合素的调控表达与功能。通过CD11c/CD18与纤维蛋白原结合和触发增殖之间的关系。
J Exp Med. 1991 Dec 1;174(6):1313-22. doi: 10.1084/jem.174.6.1313.
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Effect of donor and recipient immunization protocols on primary and secondary human antibody responses in SCID mice reconstituted with human peripheral blood mononuclear cells.供体和受体免疫方案对用人外周血单个核细胞重建的重症联合免疫缺陷(SCID)小鼠的初次和二次人抗体反应的影响。
Infect Immun. 1992 Jun;60(6):2305-8. doi: 10.1128/iai.60.6.2305-2308.1992.
3
Identification of a novel surface protein on activated CD4+ T cells that induces contact-dependent B cell differentiation (help).
鉴定活化CD4⁺T细胞上一种诱导接触依赖性B细胞分化(辅助作用)的新型表面蛋白。
J Exp Med. 1992 Apr 1;175(4):1091-101. doi: 10.1084/jem.175.4.1091.