|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1997 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1996 : ¥1,100,000 (Direct Cost : ¥1,100,000)
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.