1995 Fiscal Year Final Research Report Summary
Analysis of mutant mice lacking Vpre-B3 (8HS-20) gene encoding a third surrogate light chair.
| Project/Area Number |
06670366
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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 |
Immunology
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| Research Institution | National Institute of Health ofJapan |
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Principal Investigator |
KIMOTO Hiroshi National Institute of Health of Japan Immunology, Researcher, 免疫部, 研究員 (20225080)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEMORI Toshitada National Institute of Health of Japan Immunology, director of the department, 免疫部, 部長 (60114295)
KASIWADA Masaki National Institute of Health of Japan Immunology, Rearcher, 免疫部, 研究員 (20270639)
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| Project Period (FY) |
1994 – 1995
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| Keywords | B cell differentiation / mu chain complex / lambda 5 / Vper-B1 / T dependent antigen / gene targeting / surrogate loght chain / mice lacking Vpre-B3 (8HS-20) gene |
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| Research Abstract |
Mu chains associate with lambda 5 and Vpre-B1 surrogate light chains in pro-B and pre-B cells.Mu/surrogate light chain complex play a critical role in B cell proliferation and differentiation including allelic exclusion.We have isolated the gene, Vpre-B3, encoding for the third surrogate L chain.The Vpre-B3 gene was expressed in bone marrow B cells and, albeit at low level, in splenic B cells.The VpreB-3 product transiently associated with mu chains after their synthesis and was replaced with Vpre-B1 and lambda 5 later in pre-B cell lymphomas.In order to analyze the role of Vpre-B3 in B cell differentiation, we have established Vpre-B3 knock out mice under the collaboration with Dr.Rajewsky in Cologne, FRG.The numnber of B cells in the bone marrow and spleen was indistinguishabkle in Vpre-B3 knock out and the control mice ; however, the frequency of HSAhi or CD23 hi B cell subpopulation was higher in the knock out mice, but not all of the mice examined, than that control mice.In addition, we observed that the level oflgG2a antibody response to NP-CG in the immuniged knock out mice was 2-3 times higher than that of the control mice.Because the knock out mice carry the genetic bacground of 129 and C57BL/6, we have back-crossed the mice to C57BL/6 mice and establisehd N6.We are now re-analysing the phenotype of B cell population and immune response in N6 knock out mice.In addition, we have established the lambda 5 and VpreB-3 double knock out mice in ordre to
know the role of Vpre-B3 in early B cell development.
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