1997 Fiscal Year Final Research Report Summary
Isolation of apoptosis-related genes induced by CD40 ligation
| Project/Area Number |
08839018
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
免疫の制御機構
|
|---|
| Research Institution | KYUSHU UNIVERSITY |
|---|
Principal Investigator |
WANG Jiyang MEDICAL INSTITUTE OF BIOREGULATION,KYUSHU UNIVERSITY,RESEARCH ASSOCIATE, 生体防御医学研究所, 助手 (80231041)
|
|---|
| Project Period (FY) |
1996 – 1997
|
| Keywords | Anti-IgM antibody / B lymphocyte / Fas expression / Apoptosis / CD40 / CD40 ligand |
|---|
| Research Abstract |
We have found that Fas expression in B cells can be strongly induced by CD40 ligation but not by anti-IgM stimulation of IL-4. We also demonstrated that the susceptibility to Fas-mediated apoptosis of B cells is enhanced by CD40 crosslinking but decreased by treatment with anti-IgM antibodies. Using semi-quantitative RT PCR analysis of total RNA from CD40-activated splenic B cells, we could not find a good correlation between the enhanced Fas susceptibility in B cells stimulated by CD40L and the expression of a couple of apoptosis-related genes including HCP,RIP,FADD and ICE.While CD40 ligation did not affect the expression of bcl-2, bcl-xL and bax, anti-IgM treatment strongly induced bcl-xL expression without altering the expression of bcl-2 or bax. Using a subtractive screening strategy, we have successfully isolated a novel cDNA encoding a 587 a.a.protein. This novel protein contains 15 zinc finger motifs which may form a DNA-binding domain, and an acidic domain at its N-terminal which is a potentially transcriptional activation domain. In addition, we have also succeeded in isolating two other novel genes that are induced by CD40L alone or CD40L plus anti-IgM,respectively. We are currently investigating the potential roles of these novel genes in the B cell activation, Fas induction and Fas-triggered apoptosis, as well as the generation of memory B cells.
|
