Analysis of the mechanism of mature B cell differentiation controlled by survival signals from BCR and BAFF-R

BCR和BAFF-R生存信号控制成熟B细胞分化的机制分析

• 批准号: 23590575
• 负责人: SASAKI YOSHITERU
• 金额: $ 3.41万
• 依托单位: Kyoto University (2012-2013)The Institute of Physical and Chemical Research (2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590575/
• 关键词: B細胞; シグナル伝達; 遺伝子改変マウス; NF-kB

Signals from BCR and BAFF-R control the differentiation of mature B cells as well as their survival. In this research I investigated the roles of signals from BCR and BAFF-R in the differentiation of mature B cells and found that Akt, one of the target molecule of PI3 kinase, which transmits the survival signal from BCR plays an important role in B1 cell development and that the main function of the canonical NF-kappaB pathway in the generation of mature B2 and MZ B cells is the control of the strength of BAFF-R mediated alternative NF-kappaB signaling. I also examined the function of a novel ubiquitin ligase complex, LUBAC in B cells and discovered that LUBAC plays important roles in the development of B1 cells and the antibody responses and is required for the activation of the canonical NF-kappaB pathway by CD40 and TACI but not by BCR.

来自BCR和BAFF-R的信号控制成熟B细胞的分化和存活。在这个研究,我调查了来自BCR信号的角色和BAFF-R成熟B细胞的分化,发现一种蛋白激酶,PI3激酶的目标分子之一,传送的生存信号BCR扮演重要的角色在B1细胞发展和规范化的主要功能NF-kappaB通路的一代成熟的B2和MZ B细胞的控制替代NF-kappaB BAFF-R介导信号的强度。我还研究了一种新的泛素连接酶复合物LUBAC在B细胞中的功能，发现LUBAC在B1细胞的发育和抗体反应中起着重要作用，并且是CD40和TACI激活典型NF-kappaB途径所必需的，而不是由BCR激活。

项目成果

Canonical NF-κB pathway controls the strength of BAFF-R signaling through the induction of p100NF-κB2

经典 NF-κB 通路通过诱导 p100NF-κB2 控制 BAFF-R 信号强度

• 发表时间: 2011
• 作者: 大洞将嗣;黒崎知博;佐々木義輝
• 通讯作者: 佐々木義輝

Defective immune reponses in mice lacking LUBAC-mediated linear ubiquitination in B cells

B 细胞中缺乏 LUBAC 介导的线性泛素化的小鼠的免疫反应有缺陷

• 发表时间: 2013
• 期刊: EMBO J .
• 作者: Sasaki;Y.;Sano;S.;Nakahara;M.;Murata;S.;Kometani;K.;Aiba;Y.;Sakamoto;S.;Watanabe;Y.;Tanaka;K.;Kurosaki;T. and Iwai;K.
• 通讯作者: K.

Canonical NF-kB pathway controls the strength of BAFF-R signaling through the induction of p100NF-kB2

规范 NF-kB 通路通过诱导 p100NF-kB2 控制 BAFF-R 信号强度

• 作者: 大洞将嗣;高柳広;佐々木 義輝
• 通讯作者: 佐々木 義輝

Defective immune reponses in mice lacking LUBAC-mediated linear ubiquitination in B cells.

B 细胞中缺乏 LUBAC 介导的线性泛素化的小鼠的免疫反应有缺陷。

• 发表时间: 2013
• 期刊: EMBO Journal
• 影响因子: 11.4
• 作者: Sasaki;Y.;Sano;S.;Nakahara;M.;Murata;S.;Kometani;K.;Aiba;Y.;Sakamoto;S.;Watanabe;Y.;Tanaka;K.;Kurosaki;T. and Iwai;K.
• 通讯作者: K.

B細胞の発生・機能における直鎖状ポリユビキチン鎖の機能解析

B 细胞发育和功能中线性多聚泛素链的功能分析

• 发表时间: 2013
• 作者: Yoshikawa;S.;Egawa;M.;Oh-hora;M.;Adachi;T.;Horiguchi;K.;Li;L.;Ohta;T.;Kawano;Y.;Minagishi;Y. and Karasuyama;H.;佐々木義輝
• 通讯作者: 佐々木義輝