CORRECTION OF GLD AUTOIMMUNITY BY CO-INFUSION OF NORMAL BONE-MARROW SUGGESTS THAT GLD IS A MUTATION OF THE FAS LIGAND GENE

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.