Through an ITIM-Independent Mechanism the Fc gamma RIIB Blocks B Cell Activation by Disrupting the Colocalized Microclustering of the B Cell Receptor and CD19
文献类型：期刊论文
| 作者 | Xu, Liling ; Li, Gen ; Wang, Jing ; Fan, Yilin ; Wan, Zhengpeng ; Zhang, Shaosen ; Shaheen, Samina ; Li, Jing ; Wang, Li ; Yue, Cai ; Zhao, Yan ; Wang, Fei ; Brzostowski, Joseph ; Chen, Ying-Hua ; Zheng, Wenjie ; Liu, Wanli |
| 刊名 | JOURNAL OF IMMUNOLOGY
 |
| 出版日期 | 2014 |
| 卷号 | 192期号:11页码:5179-5191 |
| 产权排序 | 4 |
| 通讯作者 | Liu, WL (reprint author), Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China. |
| 合作状况 | 其它 |
| 英文摘要 | B cell activation is regulated through the interplay of the BCR with the inhibitory coreceptor Fc gamma RIIB and the activating coreceptor CD19. Recent studies suggest that Ag-driven BCR microclusters are efficiently converted to a signaling active state on colocalization with CD19 microclusters. Using total internal reflection fluorescence microscopy-based, high-resolution, high-speed live-cell and molecule imaging approaches, we show that when co-ligated to the BCR, the Fc gamma RIIB can inhibit B cell activation by blocking the colocalization of BCR and CD19 microclusters within the B cell immunological synapse. Remarkably, this inhibitory function of FcgRIIB is dependent not on its well-characterized ITIM-containing cytoplasmic domain, but its transmembrane domain. Indeed, human primary B cells from systemic lupus erythematosus patients homozygous for gene encoding the loss-of-function transmembrane domain mutant Fc gamma RIIB-I232T fail to block the synaptic colocalization of the BCR with CD19, leading to dysregulated recruitment of downstream signaling molecule p-PI3K to membrane proximal signalosome. This inhibitory function of Fc gamma RIIB in impairing the spatial-temporal colocalization of BCR and CD19 microclusters in the B cell immunological synapse may help explain the hyper-reactive features of systemic lupus erythematosus patient B cells in reported studies. These observations may also provide new targets for therapies for systemic autoimmune disease. |
| 学科主题 | Immunology |
| 收录类别 | SCI |
| 语种 | 英语 |
| 公开日期 | 2016-02-26 |
| 源URL | [http://210.75.237.14/handle/351003/26681]  |
| 专题 | 成都生物研究所_天然产物研究 |
| 推荐引用方式 GB/T 7714 | Xu, Liling,Li, Gen,Wang, Jing,et al. Through an ITIM-Independent Mechanism the Fc gamma RIIB Blocks B Cell Activation by Disrupting the Colocalized Microclustering of the B Cell Receptor and CD19[J]. JOURNAL OF IMMUNOLOGY,2014,192(11):5179-5191. |
| APA | Xu, Liling.,Li, Gen.,Wang, Jing.,Fan, Yilin.,Wan, Zhengpeng.,...&Liu, Wanli.(2014).Through an ITIM-Independent Mechanism the Fc gamma RIIB Blocks B Cell Activation by Disrupting the Colocalized Microclustering of the B Cell Receptor and CD19.JOURNAL OF IMMUNOLOGY,192(11),5179-5191. |
| MLA | Xu, Liling,et al."Through an ITIM-Independent Mechanism the Fc gamma RIIB Blocks B Cell Activation by Disrupting the Colocalized Microclustering of the B Cell Receptor and CD19".JOURNAL OF IMMUNOLOGY 192.11(2014):5179-5191. |
入库方式： OAI收割
来源：成都生物研究所
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