B細胞終末分化の分子機構についての研究

B细胞终末分化的分子机制研究

• 批准号: 09836006
• 负责人: WAKATSUKI Yoshio
• 金额: $ 2.05万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09836006/
• 关键词: Immunology; B cell; differentiation; antibody; transcription factor; transgenic mouse

In order to determine in vivo function of Pax-5/BSAP, function in the regulation of antibody secretion and B cell differentiation in particular, we investigated genomic configuration of Pax-5 gene and specificity of Pax-5 promotor activity in B cells. In addition, we have created transgenic mouse in which physiological regulation of Pax-5 expression is abrogated. By doing this, we studied the effect of sustained over expression of Pax-5 at the B cell differentiation to plasma cell, the differentiation stage at which native Pax-5 expression is turned off.1, We have cloned a DNA fragment of 2Kb which spans exon 1A of Pax-5 and 5' intronic region.2, No B cell specific regulatory elements were found in this region.3, Novel region regulating B cell specific expression of Pax-5 is identified.4, Novel transcription factors regulating Pax-5 expression was discovered.5, Pax-5 transgenic mice were established. Unexpected phenotype of the mice was identified.The project is now at the stage of publication.

为了确定 Pax-5/BSAP 的体内功能，特别是在调节抗体分泌和 B 细胞分化中的功能，我们研究了 Pax-5 基因的基因组配置和 B 细胞中 Pax-5 启动子活性的特异性。此外，我们还创建了转基因小鼠，其中 Pax-5 表达的生理调节被废除。通过这样做，我们研究了Pax-5持续过度表达在B细胞分化为浆细胞时的影响，在这个分化阶段，天然Pax-5表达被关闭。1，我们克隆了一个2Kb的DNA片段，它跨越Pax-5的外显子1A和5'内含子区域。2，在该区域没有发现B细胞特异性调节元件。3，调节Pax-5的B细胞特异性表达的新区域 4、发现了调控Pax-5表达的新转录因子。5、建立了Pax-5转基因小鼠。鉴定出小鼠的意外表型。该项目目前正处于发表阶段。

项目成果

Kweon, M. N., Fujihashi, K., Wakatsuki, Y. et. Al: "Mucosally induced systemic T cell unresponsiveness to ovalbumin requires CD40 ligand-CD40 interactions"J Ummunol. 162(4). 1904-9 (1999)

Kweon，M.N.，Fujihashi，K.，Wakatsuki，Y. 等。

Usui,T、Wakatsuki,Y.,et.al: "Overexpression of B cell-specific activator protein (BSAP/Pax-5)in a late B cell is sufficient to suppress differentiation to an Ig high producer cell with plasma cell phenotype"J Immunol. 158(7). 3197-3204 (1997)

Usui, T, Wakatsuki, Y. 等人：“晚期 B 细胞中 B 细胞特异性激活蛋白 (BSAP/Pax-5) 的过度表达足以抑制分化为具有浆细胞表型的 Ig 高生产细胞”免疫学杂志 158(7)。

Yoshida, M., Wakatsuki, Y., et al: "Cloning and characterization of a novel membrane-associated antigenic protein of Helicobacter pylon"Infect Immun. 67(1). 286-93 (1999)

Yoshida, M.、Wakatsuki, Y. 等人：“幽门螺杆菌新型膜相关抗原蛋白的克隆和表征”感染免疫。

Sakata-Kaneko,S、Wakatsuki,Y、et.al: "Lysophosphatidylcholine upregulates CD40 ligand expression in newly activated human CD4+ T cells"FEBS Lett. 433(1-2). 161-165 (1998)

Sakata-Kaneko, S, Wakatsuki, Y 等人：“溶血磷脂酰胆碱上调新激活的人 CD4+ T 细胞中的 CD40 配体表达” FEBS Lett 433(1-2) (1998)。

Usui, T., Wakatsuki, Y., et. Al: "Overexpression of B cell-specific activator protein (BSAP/Pax-5) in a late B cell is sufficient to suppress differentiation to an Ig high producer cell with plasma cell phenotype"J Ummunol. 158(7). 3197-204 (1997)

臼井 T.、若月 Y. 等