1999 Fiscal Year Final Research Report Summary
Mechanism of B cell proliferation and diffentiation in peripheral lymphoid organs
| Project/Area Number |
10670313
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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 |
Immunology
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| Research Institution | Research Institue for Microbial Diseases, Osaka University |
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Principal Investigator |
KAISHO Tsuneyasu Osaka Univ., Res. Inst. For Microbial Diseases, Associate Professor, 微生物病研究所, 助教授 (60224325)
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| Project Period (FY) |
1998 – 1999
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| Keywords | peripheral lymphoid organ / B cell / follicular dendritic cell / gene targeting |
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| Research Abstract |
B cell development in peripheral lymphoid organs requires an intimate interaction with follicular dendritic cells (FDC). FDC provides antigens, chemokines, and cyokines, which support B cell growth and differentiation. Then, transcriptional machinery including NF-kappaB is activated. This study aims to clarify these steps in vivo mainly by using gene targeting approach.
1. FDC produces a chemokine, BLC, which is known to act on mature B cells in vitro. In order to clarify its in vivo roles, we have established BLC-deficient mice. BLC-deficient mice were born healthy. We plan to analyze B cell distribution in peripheral lymphoid organs, FDC differentiation, and immune responses in BLC-deficient mice.
2. Both IkappaB kinase (IKK) alpha and beta activate NF-kappaB activities, which are critical for B cell growth and differentiation. Although these two kinases shows similar molecular structures and functions, they are differentially required for various tissues. IKKalpha-deficient mice die soon after birth because of limb and epidermis malformation. In order to analyze how IKKalpha plays critical roles in B cells, we have established IKKalpha-deficient chimeric mice by transferring IKKalpha-deficient fetal liver cells into irradiated mice. IKKalpha-deficient chimeras showed decrease of mature B cell population mainly through enhanced apoptosis. They also showed severe impairment of immunoglobulin production and immune response. The results suggest that IKKalpha is essential for B cell growth and differentiation in peripheral lymphoid organs and that IKKbeta alone cannot properly activate NF-kappaB in mature B cells.
3. We have established the mutant mice lacking a transcription factor, C/EBPgamma. C/EBPgamma-deficient natural killer (NK) cells showed impairment of NK activity and interferon-gamma production. Novel gene(s) were assumed to be involved in C/EBPgamma-mediated NK activity. Identification of the target gene of C/EBPgamma is now in progress.
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