1998 Fiscal Year Final Research Report Summary
Analysis for molecular and cellular mechanism regulating differentiation, activation and programmed cell death of B lymphocytes.
| Project/Area Number |
08407012
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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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) |
WANG Jiyang CHIBA CANCER CENTER RESEARCH INSTITUTE,DIVISION OF PATHOLOGY,RESEARCHER, 病理研究部, 研究員 (80231041)
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| Project Period (FY) |
1996 – 1998
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| Keywords | antigen receptor / tyrosine kinase / autoimmunity / tolerance / apoptosis / knockout mouce / G-protein / signal transduction |
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| Research Abstract |
Transmembrane signal transduction initiated by the B cell antigen receptor (BCR) is essential for various B cell activities, including cell activation, proliferation, anergy and deletion. Signaling through the BCR primarily drives mature B cells into proliferation leading to the expansion of antigen-specific clones. In contrast, immature lymphocytes usually undergo apoptosis, rather than proliferation, upon triggering through BCR.This is the foundation for negative selection, a process that ensures the generation of a self-tolerant immune repertoire during lymphocyte development.
(1) We established Lyn-kinase-deficient mice with immunoglobulin genes encoding an autoantibody against mouse RBC.We demonstrated by using this system a crucial role of Lyn kinase in regulating peripheral B cell tolerance and in preventing autoantibody production.
(2) Affinity maturation in Lyn-deficient mice with defective germinal denter formation. One of the phenotypes observed in lyn-/- mice was a defect in the ability to form germinal centers (GCs). We clarify whether affinity maturation could occur in lyn-/- mice. We shows that the affinity of Abs produced was comparable to that in wild type mice.
(3) The death signals from B cell antigen receptor target mitochondria, activating necrotic and apoptotic death cascade in a murine B-cell line, WEHI-23I cell. The present works revealed that caspases are activated through BCR signaling to cause apoptosis but mitochondrial alterations and plasma membrane dysfunction, which were also induced by BCR signaling, are not related to the caspase activities. Mitochondrial dysfunction appeared to proceed prior to the plasma membrane and nuclear changes.
(4) We showed the first direct evidence of a cross-talk between G-protein mediated signal pathway and antigen-receptor mediated signal transduction pathway in T and B cells.
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