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 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.
Matsumoto
A K
AK
Division of Molecular and Clinical Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Martin
D R
DR
Carter
R H
RH
Klickstein
L B
LB
Ahearn
J M
JM
Fearon
D T
DT
D015703:Antigens, CD / Q000737:chemistry / Q000502:physiology*; D018941:Antigens, CD19; D000943:Antigens, Differentiation / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D017463:Receptors, Complement 3b / Q000502:physiology; D017464:Receptors, Complement 3d / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D060225:Tetraspanin 28; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018941:Antigens, CD19; D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D011993:Recombinant Fusion Proteins; D060225:Tetraspanin 28; C062010:leu-13 antigen