Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes.
Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes.
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B淋巴细胞的CD21/CD19/TAPA-1/LEU-13复合物的功能解剖。
DOI：
10.1084/jem.178.4.1407
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发表时间：
1993-10-01
影响因子：
15.3
通讯作者：
Fearon, D T
中科院分区：
文献类型：
--
作者：
Matsumoto, A K;Martin, D R;Carter, R H;Klickstein, L B;Ahearn, J M;Fearon, D T
B淋巴细胞的CD21/CD19/TAPA-1复合物通过膜免疫球蛋白（mIg）放大信号转导，募集磷脂酰肌醇3-激酶（pi3 -激酶），诱导同型细胞聚集。该复合物在已知的免疫系统膜蛋白复合物中是独一无二的，因为它的成分代表不同的蛋白质家族，并且可以单独表达。通过构建嵌合分子，用HLA-A2和CD4取代CD19和CD21的细胞外、跨膜和细胞质区域，我们已经确定CD19和TAPA-1通过它们的细胞外结构域相互作用，CD19和CD21通过它们的细胞外和跨膜结构域相互作用，在一个单独的复合物中，CD21和CD35通过它们的细胞外结构域相互作用。不与CD21或TAPA-1相互作用的CD19嵌合形式在Daudi B淋巴母细胞样细胞中表达，并被证明复制了复合物中包含的野生型CD19的两种功能：与mIgM协同相互作用以增加细胞内游离钙和酪氨酸磷酸化，并在mIgM连接后与pi3激酶的p85亚基结合。嵌合CD19缺乏野生型CD19诱导同型细胞聚集的能力，这种功能可归因于TAPA-1成分。CD21/CD19/TAPA-1复合体将独立功能的亚基聚集在一起，使B细胞能够对低浓度的抗原作出反应。
The CD21/CD19/TAPA-1 complex of B lymphocytes amplifies signal transduction through membrane immunoglobulin (mIg), recruits phosphatidylinositol 3-kinase (PI3-kinase), and induces homotypic cellular aggregation. The complex is unique among known membrane protein complexes of the immune system because its components represent different protein families, and can be expressed individually. By constructing chimeric molecules replacing the extracellular, transmembrane, and cytoplasmic regions of CD19 and CD21 with those of HLA-A2 and CD4, we have determined that CD19 and TAPA-1 interact through their extracellular domains, CD19 and CD21 through their extracellular and transmembrane domains, and, in a separate complex, CD21 and CD35 through their extracellular domains. A chimeric form of CD19 that does not interact with CD21 or TAPA-1 was expressed in Daudi B lymphoblastoid cells and was shown to replicate two functions of wild- type CD19 contained within the complex: synergistic interaction with mIgM to increase intracellular free calcium and tyrosine phosphorylation and association with the p85 subunit of PI3-kinase after ligation of mIgM. The chimeric CD19 lacked the capacity of the wild-type CD19 to induce homotypic cellular aggregation, a function of the complex that can be ascribed to the TAPA-1 component. The CD21/CD19/TAPA-1 complex brings together independently functioning subunits to enable the B cell to respond to low concentrations of antigen.