STUDIES ON THE DEVELOPMENT OF HUMAN B CELL LYMPHOMAS

人类 B 细胞淋巴瘤发展的研究

• 批准号: 3079466
• 负责人: LUIGI F BERTOLI
• 金额: $ 6.37万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3079466
• 关键词: B lymphocyte; antiantibody; antiidiotype antibody; bone marrow; cell population study; chromosome aberrations; chromosome disorders; clone cells; complementary DNA; cytogenetics; enzyme linked immunosorbent assay; flow cytometry; human subject; hybridomas; immunofluorescence technique; immunoglobulin genes; lymph nodes; lymphoma; monoclonal antibody; neoplasm /cancer genetics; neoplastic cell; oncogenes

We wish to test the hypothesis that the development of B cell lymphomas in humans represents a multistep process which begins in the bone marrow. This idea stemmed from studies of B and T cell malignancies in chickens and mice, and we have obtained support for it in previous studies of humans with pre-B, B and plasma cell malignancies. It contrasts with the prevailing view that B cell lymphomas arise in the lymph node; the nodular lymphomas having as their origin a subpopulation of target cells in germinal centers. In the present studies we will examine the extent of clonal involvement in patients with nodular B cell lymphomas. Cell hybridization techniques will be used to produce two types of monoclonal anti-idiotype (Id) antibodies: One specific for idiotypic determinants expressed by complete immunoglobulin molecules and others specific for V(H) idiotopes expressed on the isolated Mu heavy chains made by the B lymphoma. The former will be used to trace the distribution of the B cells belonging to the neoplastic clone in lymph node, blood and bone marrow tissue samples. The anti-V(H) Id will be used to search for members of the neoplastic clones among the pre-B cell population in the bone marrow. After determining the extent of clonal involvement, neoplastic cells and normal B cells will be isolated from each of the involved tissues and pre-B cells isolated from bone marrow. These subpopulations of cells will then be separately examined by cytogenetic techniques for chromosomal abnormalities, and restriction fragments of the cellular DNA will be analyzed with heavy and light chain gene cDNA probes to determine immunoglobulin gene rearrangements and clonality. Other studies will address the expression of cellular oncogenes in the different subpopulations. In this way we hope to learn more about the origin and the steps involved in the development of B cell lymphomas.

我们希望验证这样一种假设，即B细胞淋巴瘤的发展 人类代表着一个多步骤的过程，这个过程始于骨髓。 这一想法源于对鸡的B和T细胞恶性肿瘤的研究，以及 老鼠，我们在之前的人类研究中已经获得了支持 患有前B期、B期和浆细胞恶性肿瘤。它与 认为B细胞淋巴瘤发生在淋巴结的流行观点；结节 淋巴瘤的起源是一组靶细胞亚群 生发中心。在目前的研究中，我们将考察 结节性B细胞淋巴瘤患者的克隆性受累。细胞 杂交技术将被用来生产两种类型的单克隆 抗独特型(ID)抗体：一种针对独特型决定簇的抗体 由完整的免疫球蛋白分子和其他针对V(H)的分子表达 在分离的Mu重链上表达的独特异体 淋巴瘤。前者将用于追踪B细胞的分布 属于淋巴结、血液和骨髓中的肿瘤性克隆 组织样本。反V(H)ID将用于搜索 骨髓中前B细胞群体中的肿瘤克隆。 在确定克隆参与的程度后，肿瘤细胞和 将从每个受累组织和前B细胞中分离出正常B细胞 从骨髓中分离出的细胞。然后这些细胞亚群就会 通过细胞遗传学技术对染色体进行单独检查 细胞DNA的异常和限制片段将是 用重链和轻链基因cdna探针分析确定 免疫球蛋白基因重排与克隆性。其他研究将 解决细胞癌基因在不同肿瘤中的表达 亚群。通过这种方式，我们希望更多地了解它的起源和 与B细胞淋巴瘤的发生有关的步骤。