2006 Fiscal Year Final Research Report Summary
Study of antigen-specific B cell network in the syovial membrane of rheumatoid arthritis toward etiology-specific therapy
| Project/Area Number |
17591046
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | KYUSHU UNIVERCITY |
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Principal Investigator |
SHIOKAWA Satoshi Kyushu University, Kyushu University Hospital, Assistant Professor, 大学病院, 講師 (20215940)
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| Co-Investigator(Kenkyū-buntansha) |
MOTOMURA Seiichi Kyushu University, Medical Institute of Bioregulation, Research Associate, 生体防御医学研究所, 助手 (40304828)
IKUYAMA Shoichiro Kyushu University, Medical Institute of Bioregulation, Associate Professor, 生体防御医学研究所, 助教授 (20184393)
IKUYAMA Junji Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研, 教授 (20112336)
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| Project Period (FY) |
2005 – 2006
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| Keywords | rheumatoid arthritis / B cell / synovial membrane / antigen / rheumatoid factor / germinal center / somatic mutation / class switch |
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| Research Abstract |
Germinal center-like structures (GCLS) in the synovial membrane of the rheumatoid arthritius (RA) patients have been reported to play a role in the antigen-driven clonal proliferation of B cells.
In 2005,we microdissected the 8 GCLS from 3 synovial membrane of 2 RA patients and sequence-analyzed the γ-, μ-, and a-VH sequences. The oligoclonal B cell proliferation and stepwise accumulation of somatic mutations were observed. About 50 % of the expanded clones belonged to the VH4 family. Among the sequences of expanded clones from the different GCLS, no common VH sequence was observed. Isotype switching was not observed. These findings suggested that antigen-driven B cell response occurred in GCLS. Several antigens appeared to drive the B cells in the response and VH4 family members might play an important role.
In 2006,we performed a detailed analysis of the degree of clonal expansion and intraclonal diversity of B cells in the RA synovial membrane. For this purpose,2 or 3 small pieces were cut out from at least 2 cm separate regions of a single synovial tissue specimen and δ-VH sequences were analyzed. In 4 out of 5 patients, marked oligoclonal expansion and intraclonal diversity were observed. IgD+ B cells with somatic mutations were considered to be IgM+IgD+ memory B cells. These IgM+IgD+ memory B cells proliferated and accumulated mutations and might participate in the production of autoantibodies.
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