| Project/Area Number |
13470076
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | NATIONAL INSTITUTE OF INFECTIOUS DISEASES |
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Principal Investigator |
TAKEMORI Toshitada NATIONAL INSTITUTE OF INFECTIOUS DISEASES, DEPARTMENT OF IMMUNOLOGY, DIRECTOR, 免疫部, 部長 (60114295)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Yoshimasa NATIONAL INSTITUTE OF INFECTIOUS DISEASES, DEPARTMENT OF IMMUNOLOGY, SENIOR RESEARCHER, 免疫部, 研究員 (60311403)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2002: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | memory B cells / Germinal center / somatic mutations / survival / apoptosis / Ras / affinity selection / Bcl-6 / クローニング / 胚中心 / トランスジェニックマウス / 体細胞変異 |
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| Research Abstract |
We have previously observed that a Fas-mediated signal regulated the generation of memory B cells which heavily accumulated somatic mutations in the V_H gene at the late immune response. To examine the role of Fas in the persistence of memory B cells, memory B cells were purified from NP-primed C57BL/6 or C57BL/6-lpr/lpr mice and transferred into carrier-primed mice, followed by a challenge using a soluble NP-carrier protein administered at different intervals after cell-transfer. The result shows that NP-primed memory cells did not elicit a secondary response when transferred cells were left in the recipient for 3wks, however, NP-primed lpr memory cells responded to the secondary challenge at the same condition. Administration of anti-Fas mAbs into the recipient immediately after the transfer of normal NP-primed B cells resulted in the generation of a secondary response by challenge 3wks after the transfer. These results suggest that the Fas mediated signal negatively regulates memory persistence.
Although it is known that a deficiency in several molecules responsible for GC-formation reduces the generation of high-affinity memory B cells, the mechanism for the generation of memory B cells at the post GC-formation remains largely unknown. To examine the role of ras in memory B cell development, we have analyzed the B cell response in C57BL/6 mice who express dominant-negative ras at high levels in their B-lineage cells. Inhibition of ras activity reduced the frequency of high affinity memory cells in the spleen and impaired memory B cell activity for the secondary response. However, inhibition of Ras activity did not affect the primary response by serum antibodies, GC-formation, somatic mutations and selection of high-affinity GC and antibody-forming cells. These results suggest that ras is selectively involved in the establishment of memory B cells.
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