Es. Sobel et al., CORRECTION OF GLD AUTOIMMUNITY BY CO-INFUSION OF NORMAL BONE-MARROW SUGGESTS THAT GLD IS A MUTATION OF THE FAS LIGAND GENE, International immunology, 5(10), 1993, pp. 1275-1278
lpr and gld mice develop phenotypically indistinguishable systemic aut
oimmune diseases and marked lymphadenopathy dominated by CD4-CD8- T ce
lls. In vivo chimera experiments have demonstrated that both lpr T and
lpr B cells are intrinsically defective. Analogous experiments were c
onducted using gld mice. Lethally irradiated gld mice were given mixtu
res of congenic gld and normal (+/+) bone marrow differentially marked
by Ig heavy chain allotype. In sharp contrast to lpr- +/+ mixed chime
ras, gld- +/+ chimeras had little autoantibody production at 5 months
and minimal adenopathy at 6 months, indicating that the normal marrow-
derived cells corrected the gld defect. Thus, aberrant autoantibody pr
oduction is due to a defect extrinsic to the gld B cell and lymphoprol
iferation is due to a defect extrinsic to the gld T cell. These data s
upport the hypothesis that gld mice lack an apoptosis-inducing ligand.
The receptor for this ligand may be the Fas molecule, which is defect
ive in lpr mice.