Since Fas ligand (FasL) can induce apoptosis of Fas-bearing cells, Fas/FasL
interactions can play a critical role in maintaining self-tolerance. Fas/F
asL interactions in lupus-like autoimmune disease have been well characteri
zed in studies using either Fas or Fast mutant mice. However, the effect of
the defective Fast-mediated signaling on the establishment of lupus in oth
er mouse strains, such as NZB/W (B/W) Fl, remains uncertain. In the present
study, we examined the effect of anti-Fast monoclonal antibody (mAb) on th
e development of lupus. Treatment of B/W Fl mice with anti-Fast mAb augment
ed IgG1- and IgG2a-type anti-dsDNA Ab production. However, treatment of B/W
F1 mice with anti-Fast mAb also significantly prevented the development of
lupus nephritis. These results indicate that Fas/FasL interactions not onl
y regulate IgG-type autoantibody production, but also influence the develop
ment of lupus nephritis in B/W F1 mice. (C) 2000 Academic Press.