Heterogeneity of phenotypic expression in normal and neoplastic B-cell proliferations detected by monoclonal antibodies LN-1 and DLC-48.

Heterogeneity of phenotypic expression in normal and neoplastic B-cell proliferations detected by monoclonal antibodies LN-1 and DLC-48.
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通过单克隆抗体 LN-1 和 DLC-48 检测正常和肿瘤 B 细胞增殖中表型表达的异质性。

DOI:
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发表时间:
1988
影响因子:
3.5
通讯作者:
A. Epstein
A. Epstein
中科院分区:
医学4区
文献类型:
--
作者:
R. Marder;J. Winter;A. Epstein

文献摘要

被引文献

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最近开发的单克隆抗体 DLC-48 和 LN-1 已被证明是补体介导的人类 B 细胞细胞裂解的有效试剂。作者最初发现这些试剂可用于消除人骨髓中的恶性淋巴瘤细胞以进行自体骨髓移植。在当前的研究中,作者进一步表征了这些抗体在 B 细胞肿瘤中的反应性,并分析了良性和肿瘤性淋巴细胞中 B 细胞单克隆抗体抗原表达的异质性。通过使用定量流式细胞术技术评估抗原表达的异质性,研究结果表明,个体患者肿瘤内的许多 B 细胞相关单克隆抗体存在表型异质性,包括 B1、常见急性淋巴细胞白血病抗原 (CALLA)、Ia、Ba-1、DLC-48 和 LN-1。在给定的淋巴肿瘤组织学类别中,发现表型异质性是某些个体病例的特性,而不是所有检查的 B 细胞单克隆抗体的其他特性。这种异质性在患有相似肿瘤的患者中并没有一致地表达,也不是给定抗原的一致特性。使用源自大细胞淋巴瘤的细胞系,作者能够发现肿瘤细胞系内的表型异质性,这些异质性可用于开发在补体介导的细胞裂解背景下处理表型异质性的模型。他们还确定,对于 DLC-48 和 LN-1,异质性与增殖细胞的细胞周期阶段无关。结果表明,针对肿瘤细胞骨髓耗竭的单一单克隆抗体治疗可能不足以克服 B 细胞肿瘤的表型异质性。
Recently developed monoclonal antibodies DLC-48 and LN-1 have been shown to be effective reagents for complement-mediated cell lysis of human B-cells. The authors have initially found that these reagents are useful in elimination of malignant lymphomas cells from human bone marrow for autologous bone marrow transplantation. In the current study, the authors have further characterized the reactivity of these antibodies in B-cell neoplasia and have analyzed the heterogeneity of antigenic expression among benign and neoplastic lymphoid cells for B-cell monoclonal antibodies. With the use of quantitative flow cytometric techniques to assess heterogeneity of antigen expression, the findings indicate that phenotypic heterogeneity within neoplasms from individual patients exists for a number of B-cell-related monoclonal antibodies, including B1, common acute lymphocyte leukemia antigen (CALLA), Ia, Ba-1, DLC-48, and LN-1. Within a given histologic class of lymphoid neoplasia, phenotypic heterogeneity was found to be a property of some individual cases and not others for all B-cell monoclonal antibodies examined. This heterogeneity was not consistently expressed in patients with similar tumors, nor was it a consistent property of a given antigen. Using cell lines derived from large cell lymphomas, the authors were able to find phenotypic heterogeneity within neoplastic cell lines that can be used to develop models for dealing with phenotypic heterogeneity in the context of complement-mediated cell lysis. They also established that for DLC-48 and LN-1, the heterogeneity was not related to the phase of the cell cycle of the proliferating cells. The results suggest that single monoclonal antibody treatment for bone marrow depletion of neoplastic cell may be insufficient to overcome phenotypic heterogeneity of B-cell neoplasms.