SEARCH FOR NOVEL B CELL HYPERACTIVITY GENES

我们的长期目标是确定基因及其产物 确定 B 细胞的过度活跃，特别是 B-1（DC5 谱系）B 细胞。 新西兰黑（NZB）小鼠，具有终生寿命 将研究 B-1 细胞的过度活跃。 NZB小鼠不仅 发展为自身免疫性疾病，而且恶性疾病的发生率也很高 B-1 B 细胞淋巴瘤与人类 CLL 非常相似 艾滋病患者罹患 B 细胞淋巴瘤。 另外B-1B 类风湿性关节炎 (RA) 发炎关节中的细胞过度活跃 在抗原呈递中起主要作用的患者 炎症细胞的激活。 我们有初步证据 显示 NZB 小鼠过度活跃的 B 细胞差异表达 一些在正常 B 细胞中不表达的基因。 在这个 开发和可行性研究，我们想确认 这些 B 细胞过度活跃基因的身份。 最终我们的目标是 克隆这些差异表达基因的全长 cDNA， 对它们进行测序，研究它们的基因组组织并定义它们 功能。 对 B 细胞过度活跃基因的研究可能会揭示新的 基因或已知基因的新功能。 除了与 RA 相关之外 和如上所述的恶性 B 细胞淋巴瘤，该项目可以 加深我们对B细胞基本机制的理解 分化、信号转导、耐受性和细胞凋亡。

Our long-term goal is to identify the genes and their products that determine hyperactivity of B cells, particularly B-1 (DC5-lineage) B cells. New Zealand Black (NZB) mice, that have a life-long hyperactivity ob B-1 cells, will be studied. NZB mice not only develop autoimmune disease but also a high incidence of malignant lymphomas of B-1 B cells that are very similar to human CLL and the B cell lymphomas developing the AIDS patients. In addition B-1 B cells are hyperactive in the inflamed joints of rheumatoid arthritis (RA) patients where they play a major role in antigen presentation and activation of inflammatory cells. We have preliminary evidence showing that the hyperactive B cells of NZB mice differentially express several genes that are not expressed in normal B cells. In this development and feasibility study, we would like to confirm the identity of these B cell hyperactivity genes. Eventually we aim to clone the full length cDNA for these differentially expressed genes, sequence them, study their genomic organization and define their function. This search for B cell hyperactivity genes may reveal novel genes or new function for known genes. Besides its relevance to RA and malignant B cell lymphomas as stated above, this project could enhance our understanding of the basic mechanisms of B cell differentiation, signal transduction, tolerance and apoptosis.