STUDIES ON THE DEVELOPMENT OF HUMAN B CELL LYMPHOMAS

我们希望检验这一假设，即B细胞淋巴瘤的发展， 对人类来说，这是一个多步骤的过程，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， 我们在以前的人类研究中也得到了支持 前B、B和浆细胞恶性肿瘤。 它与 普遍认为B细胞淋巴瘤发生在淋巴结中;结节性 以靶细胞亚群为起源的淋巴瘤， 老年中心 在目前的研究中，我们将研究 结节性B细胞淋巴瘤患者的克隆性受累 细胞 杂交技术将用于产生两种类型的单克隆抗体， 抗独特型（Id）抗体：对独特型决定簇具有特异性的抗体 由完整的免疫球蛋白分子和其他V（H）特异性分子表达 由B产生的分离Mu重链上表达的独特位 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克隆 组织样本 抗V（H）Id将用于搜索 骨髓中前B细胞群中的肿瘤克隆。 在确定克隆参与的程度后，肿瘤细胞和 将从每个相关组织和前B中分离正常B细胞 从骨髓中分离的细胞。 然后这些细胞亚群将 通过细胞遗传学技术单独检查染色体 异常，细胞DNA的限制性片段将被 用重链和轻链基因cDNA探针分析以确定 免疫球蛋白基因重排和克隆性。 其他研究将 解决细胞癌基因的表达， 亚群 通过这种方式，我们希望更多地了解起源和 参与B细胞淋巴瘤发展的步骤。

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.