FUNCTIONAL DISSECTION OF THE CD21 CD19/TAPA-1/LEU-13 COMPLEX OF B-LYMPHOCYTES/

The CD21/CD19/TAPA-1 complex of B lymphocytes amplifies signal transdu ction through membrane immunoglobulin (mIg), recruits phosphatidylinos itol 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 famil ies, and can be expressed individually. By constructing chimeric molec ules replacing the extracellular, transmembrane, and cytoplasmic regio ns of CD19 and CD21 with those of HLA-A2 and CD4, we have determined t hat 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 domai ns. 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 replic ate two functions of wild-type CD19 contained within the complex: syne rgistic interaction with mIgM to increase intracellular free calcium a nd tyrosine phosphorylation and association with the p85 subunit of PI 3-kinase after ligation of mIgM. The chimeric CD19 lacked the capacity of the wild-type CD19 to induce homotypic cellular aggregation, a fun ction of the complex that can be ascribed to the TAPA-1 component. The CD21/CD19/TAPA-1 complex brings together independently functioning su bunits to enable the B cell to respond to low concentrations of antige n.