pp59fyn mutant mice display differential signaling in thymocytes and peripheral T cells.
We have generated mutant mice that do not express pp59fyn, a nonreceptor protein tyrosine kinase related to pp60src, by homologous recombination in embryonic stem cells. fyn- mice did not display an overt phenotype. Because fyn is associated with the T cell receptor (TCR), thymocyte and T cell signaling was analyzed in the mutant background. Cross-linking of TCR-CD3 in thymocytes led to markedly reduced calcium fluxes and abrogated proliferation, whereas mature splenic T cells retained largely normal proliferation despite depressed calcium movements and IL-2 production. Similarly, proliferation induced by Thy-1 cross-linking was reduced in thymocytes but not in splenic T cells. fyn- thymocytes were impaired at a late stage of maturation and showed limited clonal deletion to the Mls-1a self-super-antigen but not to staphylococcal enterotoxin A. These results implicate fyn as a critical component in TCR signaling in thymocytes and, potentially, in the process that determines T cell repertoire in the adult mouse.
Stein
P L
PL
Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030.
Lee
H M
HM
Rich
S
S
Soriano
P
P
D000818:Animals; D000906:Antibodies; D000945:Antigens, Differentiation, T-Lymphocyte; D001483:Base Sequence; D017252:CD3 Complex; D002454:Cell Differentiation; D002478:Cells, Cultured; D015759:Ionomycin; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010703:Phorbol Esters; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000648:ultrastructure
D000906:Antibodies; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D010703:Phorbol Esters; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D015759:Ionomycin; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn