| Project/Area Number |
63570169
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Juntendo University |
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Principal Investigator |
HIROSE Sachiko Juntendo University, Pathology, Associate Professor, 医学部, 助教授 (00127127)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Takashi Juntendo University, Pathology, Instructor, 医学部, 助手 (20185440)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | New Zealand mice / Systemic lupus erythematosus / Major histocompatibility complex / T cell receptor / Anti-DNA antibody / Congenic New Zealand mice / Class II molecule / ニュージーランドマウス / 全身性エリテマトーデス / 主要組織適合遺伝子複合体 / コンジェニックマウス |
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| Research Abstract |
As compared with the NZB strain, NZB x NZW F1 (B/W F1) hybrid mice show a much earlier onset and a higher incidence of renal disease, associated with markedly increased serum levels of anti-DNA antibodies. The increment of anti-DNA antibodies is mainly due to the increase in IgG class antibodies. These events in the B/W F1 mice can be attributed to the contribution of genes derived from both NZB and nonautoimmune NZW strains. Our studies using H-2 congenic New Zealand mice suggested that both H-2^d from NZB mice and H-2^z from NZW mice were required for IgG anti-DNA antibody production in B/W F1 mice. Our data also suggested that the gene linked to the T cell receptor beta chain gene complex of NZW has an important role in this event. The in vitro studies revealed that IgG anti-DNA antibody production in B/W F1 mice is strictly dependent on the interaction of antibody producing B cells and CD4^+ helper T cells. Together with these genetical and cellular studies, it is strongly suggested that the interplay between the hybrid Ia molecules derived from both NZB and NZW on B cells and T cell receptor from NZW may be essential for the production of IgG anti-DNA antibodies in B/W F1 mice.
The requirement of H-2 heterozygosity for IgG anti-DNA antibody production was confirmed by the studies using H-2 congenic New Zealand mice, which we have already established. We are now trying to establish T cell receptor beta chain congenic New Zealand mice and to confirm the important role of T cell receptor for IgG anti-DNA antibody production in both in vivo and in vitro systems.
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