SEARCH FOR NOVEL B CELL HYPERACTIVITY GENES

我们的长期目标是识别出那些 确定B细胞，特别是B-1（DC 5-谱系）B的过度活性 细胞 新西兰黑（NZB）小鼠，具有终身 将研究过度活跃的ob B-1细胞。 NZB小鼠不仅 发展自身免疫性疾病，而且恶性发病率高， 与人CLL非常相似的B-1 B细胞的淋巴瘤， 艾滋病患者发生的B细胞淋巴瘤。 此外，B-1 B 类风湿性关节炎（RA）的炎症关节中的细胞过度活跃 在抗原呈递中起主要作用的患者， 激活炎症细胞。 我们有初步证据 显示NZ B小鼠的过度活跃的B细胞差异表达 在正常B细胞中不表达的几种基因。 在这 发展和可行性研究，我们想确认， 这些B细胞过度活跃基因的同一性。 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，研究它们的基因组结构， 功能 对B细胞过度活跃基因的研究可能揭示新的 基因或已知基因的新功能 除了与RA相关外， 和恶性B细胞淋巴瘤如上所述，该项目可以 提高我们对B细胞的基本机制的认识 分化、信号转导、耐受和凋亡。

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.