title: Correction of gld autoimmunity by co-infusion of normal bone marrow suggests that gld is a mutation of the Fas ligand gene.
abstract: lpr and gld mice develop phenotypically indistinguishable systemic autoimmune diseases and marked lymphadenopathy dominated by CD4-CD8- T cells. In vivo chimera experiments have demonstrated that both lpr T and lpr B cells are intrinsically defective. Analogous experiments were conducted using gld mice. Lethally irradiated gld mice were given mixtures of congenic gld and normal (+/+) bone marrow differentially marked by Ig heavy chain allotype. In sharp contrast to lpr-(+)/+ mixed chimeras, 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 production is due to a defect extrinsic to the gld B cell and lymphoproliferation is due to a defect extrinsic to the gld T cell. These data support the hypothesis that gld mice lack an apoptosis-inducing ligand. The receptor for this ligand may be the Fas molecule, which is defective in lpr mice.
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill 27599-7280.
authors.forename: E S
authors.initials: ES
authors.lastname: Sobel
authors.forename: V N
authors.initials: VN
authors.lastname: Kakkanaiah
authors.forename: P L
authors.initials: PL
authors.lastname: Cohen
authors.forename: R A
authors.initials: RA
authors.lastname: Eisenberg
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000235:genetics*; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D019014:fas Receptor
chemical_list: D000954:Antigens, Surface; D015704:CD4 Antigens; D016827:CD8 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019014:fas Receptor