SEARCH FOR NOVEL B CELL HYPERACTIVITY GENES

我们的长期目标是识别出 确定B细胞，特别是B-1(DC5-谱系)B细胞的过度活动 细胞。新西兰黑(NZB)小鼠，拥有一生的 B-1细胞的过度活动，将被研究。NZB小鼠不仅 发生自身免疫性疾病的同时也是恶性疾病的高发人群 与人类CLL非常相似的B-1B细胞淋巴瘤 B细胞淋巴瘤发生于艾滋病患者。此外，B-1B 类风湿性关节炎(RA)炎症关节中细胞过度活跃 他们在抗原提呈中起主要作用的患者 炎症细胞的激活。我们有初步证据 提示NZB小鼠高活性B细胞差异表达 几个在正常B细胞中不表达的基因。在这 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，研究它们的基因组组织，并确定它们的 功能。对B细胞过度活跃基因的研究可能揭示出新的 基因或已知基因的新功能。除了与RA相关之外 和恶性B细胞淋巴瘤如上所述，这个项目可以 加深对B细胞基本机制的认识 分化、信号转导、耐受和细胞凋亡。

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.