| Project/Area Number |
11670188
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Saitama Medical School |
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Principal Investigator |
KAYANO Hidekazu Saitama Medical School, Department of Pathology, Lecturer, 医学部, 講師 (40169652)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Hitoshi Saitama Medical School, Department of Pathology, Associate professor, 医学部, 助教授 (70137826)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | B-cell leukemias / B-cell lymphoma / immunoglobulin / somatic mutation / isotype switch / transcription / PCR / de-methylation / クラススイッチ / 転写調節 |
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| Research Abstract |
Isotype switch (IS) of immunoglobulin (Ig) heavy chain is essential for B-cell maturation. In this study we analyzed IS events on neoplastic B-cells of mature B-cell leukemias (MBL) mainly from hairy cell leukemia (HCL) and its variant (HCLv).
(1) MBL cells other than follicular lymphoma cells could undergo IgE-switch induced by anti-CD40 antibody stimuli.
(2)HCL and HCLv express Ig heavy chains in a divergent pattern. Hairy cells were analyzed for the presence of de-methylation of promoter sequence of IS-related genes that may indicate their activities. The cyclin D1 promoter sequence was de-methylated in 50% of HCL but none of HCLv. While de-methylation of the PAX5 promoter sequence was found in 16% of HCL and 67% of HCLv, suggesting difference in activation state between HCL and HCLv, although patterns of expression of Ig heavy and light chains were not different between HCL and HCLv.
(3)Somatic mutation analysis of Ig-heavy chain (VH) genes of hairy cells showed correlation between IgG expression and VH mutation frequency. The expression of Ig lambda chain was also correlated with VH mutation frequency. Thus, it is suggested that the mutation activity of the VH gene have influence on Ig expression of hairy cells.
(4)In contrast, mutation analysis of Ig light chain (VL) genes of hairy cells showed no correlation between VL and VH mutation frequency, or the expression patterns of Ig heavy or light chains, suggesting the expression of Ig light chains on hairy cells are regulated by transcription or translation but not the genetic level.
Collectively, the expression of Ig chains on hairy cells may reflect different stages of B-maturation and/or activation. HCL/HCLv may provide a human model for the pathway of B-cell maturation.
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