生发中心
CD40
B细胞
泛素连接酶
B细胞受体
生物
细胞生物学
B细胞淋巴瘤
受体
NF-κB
信号转导衔接蛋白
分子生物学
化学
癌症研究
信号转导
泛素
淋巴瘤
免疫学
抗体
生物化学
细胞毒性T细胞
体外
基因
作者
Guilin Qiao,Minxiang Lei,Zhenping Li,Yonglian Sun,Andrew W. Minto,Yang Xin Fu,Haiyan Ying,Richard J. Quigg,Jian Zhang
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2007-10-01
卷期号:179 (7): 4473-4479
被引量:35
标识
DOI:10.4049/jimmunol.179.7.4473
摘要
Abstract It has been documented that CD40 is essential for B cell function. Casitas-B-lineage lymphoma protein-b (Cbl-b), an adapter protein and ubiquitin ligase, has been shown to regulate the activation of T and B cells through their Ag receptors. In this study, we report that CD40-induced B cell proliferation is significantly augmented in mice lacking Cbl-b. Furthermore, Cbl-b−/− mice display enhanced thymus-dependent Ab responses and germinal center formation, whereas introduction of CD40 deficiency abolishes these effects. Hyper thymus-dependent humoral response in Cbl-b−/− mice is in part due to an intrinsic defect in B cells. Mechanistically, Cbl-b selectively down-modulates CD40-induced activation of NF-κB and JNK. Cbl-b associates with TNF receptor-associated factor 2 upon CD40 ligation, and inhibits the recruitment of TNF receptor-associated factor 2 to the CD40. Together, our data suggest that Cbl-b attenuates CD40-mediated NF-κB and JNK activation, thereby suppressing B cell responses.
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