CIN85 drives B cell responses by linking BCR signals to the canonical NF-kappaB pathway.
CIN85 drives B cell responses by linking BCR signals to the canonical NF-kappaB pathway.
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DOI：
10.1084/jem.20102665
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发表时间：
2011-07-04
期刊：
影响因子：
--
通讯作者：
Kurosaki T
中科院分区：
文献类型：
--
作者：
Kometani K;Yamada T;Sasaki Y;Yokosuka T;Saito T;Rajewsky K;Ishiai M;Hikida M;Kurosaki T
CIN85将B细胞受体信号转导至IKK-β，其在B细胞中的表达是小鼠非T细胞非依赖性II型抗体应答所必需的。CIN85是一种连接酪氨酸磷酸化Cbl和Cbl-b C-末端结构域的接头蛋白，被认为参与了受体的内化和随后的降解。然而，它的生理功能仍不清楚。为了确定它在B细胞中的作用，我们使用Mb1-cre产生了B细胞特异性CIN85缺失的小鼠。这些小鼠体内T细胞非依赖性II型抗体反应受损，体外对B细胞受体(Bcr)交联物的IKK-β活性和细胞反应减弱。在基因突变的小鼠中，引入了具有结构性活性的IKK-β结构，纠正了缺陷的抗体反应和细胞反应。综上所述，我们的结果表明，CIN85将bcr与IKK-β激活联系起来，从而促进T细胞非依赖性免疫反应。
CIN85 transduces B cell receptor signals to IKK-β, and its expression in B cells is essential for T cell–independent type II antibody responses in mice. CIN85, an adaptor protein which binds the C-terminal domain of tyrosine phosphorylated Cbl and Cbl-b, has been thought to be involved in the internalization and subsequent degradation of receptors. However, its physiological function remains unclear. To determine its role in B cells, we used Mb1-cre to generate mice with a B cell–specific deletion of CIN85. These mice had impaired T cell–independent type II antibody responses in vivo and diminished IKK-β activation and cellular responses to B cell receptor (BCR) cross-linking in vitro. Introduction of a constitutively active IKK-β construct corrected the defective antibody responses as well as cellular responses in the mutant mice. Together, our results suggest that CIN85 links the BCR to IKK-β activation, thereby contributing to T cell–independent immune responses.
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影响因子：
20.3
作者：
Navarro, Maria N.;Nusspaumer, Gretel;Toribio, Maria L.
通讯作者：
Toribio, Maria L.
DOI：
10.1084/jem.20062571
发表时间：
2007-09-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Anderson SM;Tomayko MM;Ahuja A;Haberman AM;Shlomchik MJ
通讯作者：
Shlomchik MJ
影响因子：
30.5
作者：
Guinamard, R;Okigaki, M;Ravetch, JV
通讯作者：
Ravetch, JV
影响因子：
64.5
作者：
Dustin, ML;Olszowy, MW;Shaw, AS
通讯作者：
Shaw, AS
影响因子：
32.4
作者：
Fu, C;Turck, CW;Chan, AC
通讯作者：
Chan, AC