| Project/Area Number |
16390142
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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 | The University of Tokyo |
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Principal Investigator |
MIYAKE Kensuke The University of Tokyo, Institute of Medical Science, Dep. Microbiology and Immunology, Professor, 医科学研究所, 教授 (60229812)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2006: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | innate immunity / endotoxin / Toll-like receptor / natural antibody / Lipopolysaccharide / MD-2 |
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| Research Abstract |
Antibody responses have an important role in defense against microbial infection. Two distinct antibodies were produced during infection, innate antibodies such as IgM and IgG3 and T-dependent antibodies including IgG2a and IgG2b. The former is produced in an T-independent manner in response to lipopolysaccharides or lipopeptides. In the present study, we examined how production of innate antibodies were regulated. Radioprotective 105/MD-1 is expressed on the B cell surface and structurally related to Toll-like receptors. We previously showed that RP105 is required for B cell responses to LPS. In this project, we showed that RP105 is also required for B cell response to TLR2 ligand, lipopeptide. Moreover, serum IgG3 is specifically low in RP105 mice. To reveal a mechanism by which RP105 induces serum IgG3, we studied expression of the γ3 germline transcript, which is constitutively expressed in splenic B cells. Intrerestingly, the constitutive expression of the γ3 germline transcript was impaired in RP105^<-/-> mice. Moreover, reduced serum IgG3 was also seen in MD-1^<-/-> mice and TLR2^<-/->TLR4^<-/-> mice. These results suggest that RP105/MD-1 and TLR2/4 work in concert for inducing serum IgG3. These results suggest that B cells are responding to TLR2/4 ligands without any apparent infection. Given that TLR2/4 respoind not only to microbial ligands but also to endogenous ligands, TLR2/4 and RP105/MD-1 may have a role in B cell response to endogenous self ligands as well as to microbial ligands. IgG3 was shown to be pathogenic in lupus nephritis, we are going to study roles for TLR2/4 and RP105/MD-1 in lupus nephritis.
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