The role of CD19 molecules on the differentiation into the memory B cells.
| Project/Area Number |
13671963
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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 |
病態科学系歯学(含放射線系歯学)
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| Research Institution | Tokyo Medical & Dental University |
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Principal Investigator |
KOZONO Yuko Tokyo Medical and Dental University, Dental Hospital, Research Associate, 歯学部附属病院, 助手 (30197107)
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| Co-Investigator(Kenkyū-buntansha) |
AZUMA Miyuki Tokyo Medical and Dental Univensty, Graduate School, Professor, 大学院・医歯学総合研究科, 教授 (90255654)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | CD19 / memory B cel / Cbl-b / AID / Bel / ubiquitin / Proteasome / co-stimulatory molecule / Cbl-b / Ubiquitin / proteasome / cbl-b / co-receptor / co-stimulatory molecules / proeasome |
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| Research Abstract |
Memory B cells are differentiated B cells which are acquired for ability of proliferation and for affinity maturation after stimulation through BCR and interaction with T cells. Affinity maturation is the process for developing higher affinity antibody by acquisition of somatic mutation on immunoglobrin gene and selection of B cells bearing higher affinity BCR CDI 9 is a co-receptor molecule for BCR to lower threshold of activation CDI 9 is expressed on only B cells, but not on differentiated plasma cells CD19 molecule is stimulated through associated molecules, CD21/CD35 via their liands, C3d/C3b. Co-crosslinking of BCR and CD19 on B cells upregulated costimulatory molecules, B7-1 and B7-2 (Y. Kozono et al.1998) We reported here mainly two different issues : The role of CD19 on differentiation; the novel mechanism for regulation of CD19 by Cbl-b and ubiquitin.
1. Co-crosslinking of BCR and CD19 on resting B cells upregulated mRNA of Activation-induced cytidine deaminase (AID) gene, which is a key molecule to induce class switch and somatic hypermutation of immunogloblin. Co-culture with B cells which were crosslinked with BCR and CD19 and helper T cells enhanced AID. These B cells were demonstrated to obtain somatic hypermutation. Moreover, co-cultured B cells demonstrated memory-like phenotype of Bcl-2, -6 and -XL expression pattern.
2. Co-crosslinkng of BCR and CD19 on resting B cells induced proteasome mediated CD19 proteolysis, which were rescued by lactacystin B cells from hapten immunized mice also showed similar CD19 proteolysis. CD19 proteolysis by both in vitro and in vivo stimulation was dependent on ubiquitin ligase, Cbl-b gene. CD19 on K46μ was directly ubiquinnated after co-crosslinkng as poly-ubiquitination and mono-ubiquitination. Thus, CD19, key molecule for activation of B cells might be promptly down regulated by Cbl-b-ubiquitin pathway.
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Report
(3 results)
Research Products
(9 results)
