1993 Fiscal Year Final Research Report Summary
Research on the regulatory mechanism of immunoglobulin gene expression and recombination by means of gene targeting.
| Project/Area Number |
04454208
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
WATANABE Takeshi MEDICAL INSTITUTE OF BIOREGULATION, KYUSHU UNIVERSITY, PROFESSOR, 生体防御医学研究所, 教授 (40028684)
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| Co-Investigator(Kenkyū-buntansha) |
KITAMURA Daisuke MEDICAL INSTITUTE OF BIOREGULATION, KYUSHU UNIVERSITY, ASSISTANT, 生体防御医学研究所, 助手 (70204914)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Signal transduction / Gene expression / Antigen receptor / HS1 / Enhancer / Transcriptional control / Gene targeting / HS1-deficient mouse |
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| Research Abstract |
The immunolobulin (Ig) gene expression and is recombination is strictly regulated by the function of its promoter and enhancer. Ig gene expression is also controlled by the signals given from surface antigen receptors. HS1 protein is one of the major substrates of Src-like protein tyrosine kinases and phosphorylated immediately after crosslinking of surface IgM(sIgM) on B cells. The HS1 is also tyrosine-phosphorylated upon the stimulation of T cell receptors(TCR). Our present results indicated the involvement of HS1 molecule in the signal transduction pathways through sIgM in B cells as well as TCRs in T cells. The mouse B lymphoma cell line, WEHI-231, is known to undergo apoptoic cell death upon crosslinking of sIgM by anti IgM antibodies. Variants of WEHI-231 which are resistant to anti-IgM induced apoptosis expressed a markedly reduced level of HS1 protein. Expression of human HS1 restored the ability of the cells to undergo apoptotic cell death of the variants. The HS1 deficient mice, which were enerated by the method of gene targeting, showed the impaired ability for thymic negative selection as well as the impaired apoptotic cell death of the B cells induced by the crosslinking of sIgM.Our results clearly demonstrated that HS1 is a molecule involved in the signal transduction pathway toward apoptosis that is triggered by the antigen receptors.
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