1. Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes.
- Author
-
Fischer KD, Zmuldzinas A, Gardner S, Barbacid M, Bernstein A, and Guidos C
- Subjects
- Animals, B-Lymphocyte Subsets metabolism, Bone Marrow Cells, CD4 Antigens biosynthesis, CD8 Antigens biosynthesis, Cell Differentiation physiology, Cell Line, Chimera, Mice, Proteins genetics, Proto-Oncogene Proteins deficiency, Proto-Oncogene Proteins c-vav, T-Lymphocyte Subsets metabolism, Thymus Gland cytology, B-Lymphocyte Subsets cytology, Cell Cycle Proteins, DNA-Binding Proteins, Proto-Oncogene Proteins metabolism, Receptors, Antigen, T-Cell metabolism, Signal Transduction, T-Lymphocyte Subsets cytology
- Abstract
During lymphocyte development, cellular proliferation and positive and negative selection events ensure the production of T and B lymphocytes bearing highly diverse, but self-tolerant, repertoires of antigen receptors. These processes are initiated when engagement of growth-factor receptors, or the T and B lymphocyte antigen receptors, induces tyrosine phosphorylation of specific SH2- and SH3-domain-containing cytoplasmic proteins, including Vav. Here we show that vav-/- embryonic stem cells generate only limited numbers of immature and mature T and B lymphocytes in the RAG-2 blastocyst complementation assay. Furthermore, Vav-deficient T lymphocytes showed severely impaired antigen receptor signalling. Finally, we demonstrate that Vav-dependent signalling pathways regulate maturation, but not CD4/CD8 lineage commitment, during T-cell-receptor-mediated positive selection of immature CD4+ CD8+ precursors into mature CD4+ CD8- or CD4- CD8+ T cells.
- Published
- 1995
- Full Text
- View/download PDF