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

这项研究的长期目标是确定分子 抗原依赖性刺激表面的机制 免疫球蛋白受体导致活化、增殖和 B淋巴细胞的分化。拟议研究的目标是 阐明Jun-B原癌基因的体内调控 特别强调了潜在的分子机制(S) Jun-B和c-Jun在SIG受体上的差异表达 并确定Jun-B蛋白在体内的功能。 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Tre结合复合体。(A)分子组成 SIG受体诱导的TrE结合复合体将通过 DNA亲和沉淀分析和紫外光交联。(B) 介导SIG受体的顺式作用调节元件(S)的性质 将通过对Jun-B的缺失图谱研究来确定Jun-B的激活 Jun-B启动子与介导SIG的反式调节因子(S) 用凝胶电泳法鉴定Jun-B的受体诱导作用 迁移率变化分析。(C)将使用反义寡核苷酸 特异性阻断Jun-B的体内合成，以明确 Jun-B在细胞活化、增殖和分化中的作用 B细胞的数量。拟议研究的结果将提供一个 关于SIG受体如何引起血管紧张素转换酶变化的分子解释 核基因表达，并将确定Jun-B和tre结合的作用 这种容量的络合物和“静止的”原生B的生长 淋巴细胞通过免疫球蛋白刺激。研究结果也可能为我们提供洞察力 论失调、自主、克隆性扩张的起源和本质 B细胞，如与恶性疾病有关的B细胞 淋巴细胞，并可能为控制进展提供指导 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.