REGULATION AND FUNCTION OF AP-1 IN PRIMARY B-CELLS

这项研究的长期目标是确定 表面抗原依赖性刺激的机制 免疫球蛋白受体导致激活，增殖， B淋巴细胞的分化。 拟议研究的目标是 阐明jun-B原癌基因的体内调节， 特别强调的分子机制（S）的基础 jun-B和c-jun在sIg受体上的差异表达 交联，并确定Jun-B蛋白的功能， 与B细胞活化、增殖和分化的关系。 研究还将评估相关sIg的性质和功能 受体诱导的TREE结合复合物。(A)的分子组成 将通过以下方法评估sIg受体诱导的TRE结合复合物 DNA亲和沉淀分析和UV光交联。(B)的 介导sIg受体的顺式作用调节元件的性质 jun-B的激活将通过缺失作图研究来鉴定， jun-B启动子和介导sIg的反式作用调节因子 将通过电泳鉴定jun-B的受体诱导 移动性变化分析(C)将使用反义寡脱氧核苷酸 特异性阻断Jun-B的体内合成， Jun-B在活化、增殖和分化中的作用 B细胞。 这项研究的结果将提供一个 关于sIg受体如何诱导 核基因表达，并将确定Jun-B和TRE-binding的作用 复合物在这种能力和"休息"的主要B的增长 通过sIg刺激的淋巴细胞。 研究结果还可能提供一些见解， 关于失调的起源和本质， B细胞，如与恶性疾病相关的那些， 淋巴细胞，并可能提供控制进展的指导 这种与B细胞相关的失调。

The long term goal of this research is to ascertain the molecular mechanisms by which antigen-dependent stimulation of the surface immunoglobulin receptor leads to the activation, proliferation, and differentiation of B lymphocytes. The goal of the proposed study is to elucidate the in vivo regulation of the jun-B proto-oncogene, with particular emphasis on the molecular mechanism(s) underlying the differential expression of jun-B and c-jun upon sIg receptor crosslinking, and to ascertain the function of the Jun-B protein in relation to B cell activation, proliferation and differentiation. Studies will also assess the nature and function of the related sIg receptor-induced TRE-binding complexes. (A) The molecular composition of the sIg receptor-induced TRE-binding complexes will be assessed by DNA-affinity precipitation analysis and UV photo-crosslinking. (B) The nature of the cis-acting regulatory element(s) that mediate sIg receptor activation of jun-B will be identified by deletion mapping studies of the jun-B promoter and the trans-acting regulatory factor(s) that mediate sIg receptor-induction of jun-B will be identified by electrophoretic mobility shift analysis. (C) Antisense oligodeoxynucleotides will be used to specifically block the in vivo synthesis of Jun-B in order to define the role of Jun-B in the activation, proliferation, and differentiation of B cells. The results of the proposed research will provide a molecular explanation regarding how sIg receptors induce alterations in nuclear gene expression and will define the role of Jun-B and TRE-binding complexes in this capacity and in the growth of "resting" primary B lymphocytes stimulated through sIg. The results may also provide insight on the origin and nature of dysregulation, autonomous, clonal expansions of B cells, such as those associated with malignant diseases of lymphocytes, and may provide a directive for controlling the progression of such B cell-associated dysregulation.