CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand
CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand
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DOI：
10.1038/ni1547
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发表时间：
2008-01-01
影响因子：
30.5
通讯作者：
Batista, Facundo D.
中科院分区：
文献类型：
--
作者：
Depoil, David;Fleire, Sebastian;Batista, Facundo D.
在这里，我们描述了时空结构，在高分子分辨率，受体和信号分子在小鼠B细胞激活的早期事件。在响应膜结合配体刺激时，抗原聚集发生在含有免疫球蛋白（Ig） M和IgD的B细胞抗原受体（BCR）微簇中，这些微簇募集Syk激酶并短暂地与辅助受体CD19结合。出乎意料的是，缺乏cd19的B细胞在bcr依赖性信号的启动、下游效应物的积累和细胞扩散方面存在显著缺陷，这些缺陷最终导致微团簇形成减少。因此，我们定义了BCR“信号体”主要成分组装的动力学，并揭示了CD19独立于共刺激分子CD21，在响应膜结合配体刺激时放大早期B细胞激活事件中的重要作用。
Here we describe the spatiotemporal architecture, at high molecular resolution, of receptors and signaling molecules during the early events of mouse B cell activation. In response to membrane-bound ligand stimulation, antigen aggregation occurs in B cell antigen receptor (BCR) microclusters containing immunoglobulin (Ig) M and IgD that recruit the kinase Syk and transiently associate with the coreceptor CD19. Unexpectedly, CD19-deficient B cells were significantly defective in initiation of BCR-dependent signaling, accumulation of downstream effectors and cell spreading, defects that culminated in reduced microcluster formation. Hence, we have defined the dynamics of assembly of the main constituents of the BCR 'signalosome' and revealed an essential role for CD19, independent of the costimulatory molecule CD21, in amplifying early B cell activation events in response to membrane-bound ligand stimulation.