Matsumoto A K, Martin D R, Carter R H, Klickstein L B, Ahearn J M, Fearon D T
Division of Molecular and Clinical Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Exp Med. 1993 Oct 1;178(4):1407-17. doi: 10.1084/jem.178.4.1407.
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.
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），并诱导同型细胞聚集。该复合物在免疫系统已知的膜蛋白复合物中是独特的，因为其组分代表不同的蛋白家族，且能单独表达。通过构建嵌合分子，用HLA-A2和CD4的胞外区、跨膜区和胞质区替换CD19和CD21的相应区域，我们确定CD19和TAPA-1通过其胞外结构域相互作用，CD19和CD21通过其胞外区和跨膜区相互作用，并且在一个单独的复合物中，CD21和CD35通过其胞外区相互作用。一种不与CD21或TAPA-1相互作用的CD19嵌合形式在Daudi B淋巴母细胞中表达，并被证明可复制复合物中野生型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，以及在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，该复合物的这一功能可归因于TAPA-1组分。CD21/CD19/TAPA-1复合物将独立发挥功能的亚基聚集在一起，使B细胞能够对低浓度抗原作出反应。
