Induction of tolerance to a soluble antigen following irradiation and bone marrow reconstitution.
Antigen-specific tolerance was induced in mice by lethal irradiation followed by reconstitution with syngeneic, anti-T-cell-treated bone marrow and injection of the protein antigen lysozyme. Animals tolerized with lysozyme responded normally to a second antigen, sheep red blood cells, and animals treated with the same tolerizing regimen using a different protein antigen, bovine serum albumin, responded normally to lysozyme. Challenge of the tolerant mice with lysozyme covalently coupled to LPS induced an antilysozyme response indicating that if tolerance was expressed on the B-cell level that antigen-specific B-cells were still present. These results eliminate clonal abortion and clonal selection as the mechanism of tolerance generation. The tolerance generated by this procedure is either expressed on the T-cell level or is produced by a state of B-cell clonal anergy which can be overcome by the use of antigen coupled to lipopolysaccharide.
D000818:Animals; D000921:Antibody-Producing Cells; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology*; D005260:Female; D006462:Hemolytic Plaque Technique; D007108:Immune Tolerance / Q000528:radiation effects*; D007113:Immunity, Innate; D007116:Immunization, Passive; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D011863:Radioimmunoassay; D012867:Skin / Q000276:immunology; D012995:Solubility
D000941:Antigens