1998 Fiscal Year Final Research Report Summary
Study of CDK inhibitors in B cell immune response
| Project/Area Number |
09044292
|
|---|
| Research Category |
Grant-in-Aid for international Scientific Research
|
| Allocation Type | Single-year Grants |
|---|
| Section | Joint Research . |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | Medical Research Intitute, Tokyo Medical and Dental University |
|---|
Principal Investigator |
TSUBATA Takeshi Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (80197756)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
RETH Michael Max Planck Institute for Immunobiology, Professor, プランク研究所, 教授
RAJEWSKY Klaus University of Cologne, Institute for Genetics, Professor, 遺伝研, 教授
AIBA Yuichi Tokyo Medical and Dental University, Medical Research Institute, Research Associ, 難治疾患研究所, 助手 (00273516)
KITAMURA Daisuke Science University of Tokyo, Research Institute for Biological Sciences, Profess, 生命科学研究所, 教授 (70204914)
ADACHI Takahiro Tokyo Medical and Dental University, Medical Research Institute, Lecturer, 難治疾患研究所, 講師 (50222625)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Keywords | B lymphocyte / cell death / CDK inhibitor / p27 / antigen receptor / c-Myc / Lyn / cell cycle |
|---|
| Research Abstract |
B lymphocytes undergo apoptosis by strong antigen receptor (BCR) crosslinking. However, CD4O signaling or CD72 ligation abrogates BCR-mediated apoptosis and induces proliferation of BCR-ligated B cells. In the B cell line WEHI-231, BCR ligation increased the level of the CDK inhibitor p27. Inducible expression of CDK inhibitors caused cell death of WEHI-231, suggesting that CDK inhibitors are involved in BCR-mediated apoptosis. In contrast, fibroblasts undergo cell cycle arrest but not apoptosis upon stimulation up-regulating CDK inhibitors. However, those stimulations induce apoptosis in-fibroblasts overexpressing c-Myc. Previously, constitutive overexpression of c-Myc was shown to block BCR-mediated apoptosis in WEHI-231. By inducibly expressing c-Myc, we showed that the previous result is an artifact and that overexpression of c-Myc enhances BCR-mediated apoptosis. Those results strongly suggest that CDK inhibitors and c-Myc play an important role in the regulation of death as well as proliferation of B cells.
When B cells survive and proliferate in the presence of CD4O signaling or CD72 ligation, the level of the CDK inhibitor p27 is reduced. We showed that CD72 is phosphorylated by Lyn and negatively regulates BCR signaling by recruiting SHP-1. Moreover, Lyn reduced the expression level of c-Myc. CD72 may thus negatively regulate c-Myc and CDK inhibitors, resulting in survival and proliferation of B cells.
|
