| Research Abstract |
In the present study, we established two kinds of gene-targeting mice.one is Lyn^deficient mice and the other, HS1-deficient mice, by applying homologous recomdination. Upon stimulation of cell surface antigen receptors on B cells, two kinds of tyrosine kinases are activated. One is src family tyosine kinasses such as Lyn, Fyn, Lck, Blk and so on. The other is Syk/ZAP70 kinase. In Lyndeficient mice, we found that the responses of the B cells were very low to the stimulation by anti-IgM,CD40 ligand and LPS.In spite of the decreased numbers of mature B cells in the periphery, splenomegaly, lymphadenopathy, hyper IgM syndrome are evident and antoantibodies were produed in Lyn-knockout mice. The mice developed finally autoimmune glomerulonephritis. HS1-deficient mice did not show autoimmune disease but the proliferative responses of B cells and T cells induced by anti-IgM or anti CD3 were impaired. Apoptosis induced by crosslinking of the surface antigen receptors was also impaired.
These results clearly indicate that Lyn-HS1 pathway plays a crucial role in signal transduction pathway from antigen-receptor complex on lymphocyte.
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