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

这项研究的长期目标是确定分子 抗原依赖性表面刺激的机制 免疫球蛋白受体导致激活、增殖和 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 特别强调潜在的分子机制 sIg受体上jun-B和c-jun的差异表达 交联，并确定 Jun-B 蛋白在 与 B 细胞活化、增殖和分化有关。 研究还将评估相关 sIg 的性质和功能 受体诱导的 TRE 结合复合物。 (A) 分子组成 sIg 受体诱导的 TRE 结合复合物将通过以下方式进行评估 DNA 亲和沉淀分析和紫外光交联。 （二） 介导 sIg 受体的顺式作用调节元件的性质 jun-B的激活将通过缺失图谱研究来确定 jun-B 启动子和介导 sIg 的反式作用调节因子 jun-B 的受体诱导将通过电泳来鉴定 流动性转变分析。 (C) 将使用反义寡脱氧核苷酸 特异性阻断 Jun-B 的体内合成，以确定 Jun-B 在激活、增殖和分化中的作用 B 细胞。 拟议研究的结果将提供 关于 sIg 受体如何诱导改变的分子解释 核基因表达并将定义 Jun-B 和 TRE 结合的作用 复合体的这种能力和“静止”初级 B 的生长 通过 sIg 刺激淋巴细胞。 结果也可能提供见解 关于失调、自主、克隆扩张的起源和性质 B 细胞，例如与恶性疾病相关的 B 细胞 淋巴细胞，并可能提供控制进展的指令 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.