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 systemicautoimmune diseases and marked lymphadenopathy dominated byCD4^–CD8^– In vivo chimera experiments have demonstratedthat both ipr T and ipr B cells are intrinsically defective.Analogous experiments were conducted using gld mice. Lethallyirradiated gld mice were given mixtures of congenic gld andnormal (+/+) bone marrow differentially marked by lg heavy chainallotype. In sharp contrast to ipr-+/+ mixed chimeras, gld-+/+chimeras had little autoantibody production at 5 months andminimal adenopathy at 6 months, indicating that the normal marrow-derivedcells corrected the gld defect. Thus, aberrant autoantibodyproduction is due to a defect extrinsic to the gld B cell andlymphoproliferation is due to a defect extrinsic to the gldT cell. These data support the hypothesis that gld mice lackan apoptosis-inducing ligand. The receptor for this ligand maybe the Fas molecule, which is defective in ipr mice T cells.