Autoimmune and lymphoproliferative disease in (B6-G IX + × 129) F 1 mice: Relation to naturally occurring antibodies against murine leukemia virus-related cell surface antigens

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Abstract
GIX congeneic mouse strains, C57BL/6-GIX+(B6-GIX+) and 129-GIX-, were derived from the prototype strains, B6(GIX-) and 129(GIX+). The hybrids, (B6-GIX+ .times. 129)F1 (GIX+F1) and (B6 .times. 129-GIX-)F1 (GIX-F1), differ only in regard to genetic loci controlling GIX antigen expression. GIX+F1 mice spontaneously produce GIX antibody and often show signs of autoimmune disease and lymphoproliferative disease. GIX-F1 mice and mice of the 2 parental strains (B6-GIX+ and 129) of GIX+F1 do not produce GIX antibody and seldom show signs of these diseases. G(ERLD) and G(RAD1), antibodies, natural thymocytotoxic autoantibody, and antinuclear antibodies were produced by GIX+F1 mice. These 4 antibodies were also found in the other strains. GIX+F1 mice develop pronounced diffuse glomerulonephritis similar to that found in systemic lupus erythematosus in man. Incidence studies in which mice were examined according to age rather than state of health showed that the lesions occurred in 38% of GIX+F1 mice but not in GIX-F1, B6-GIX+ or 129 mice. Lymphoproliferative lesions were reticulum cell sarcoma (RCS) type A or reactive lymphoid hyperplasia (RLH). RCS occurred more often in GIX+F1 (38%) than in GIX-F1 (12%) or B6-GIX+ (8%). No RCS occurred in mice of the 129 strain. RLH occurred in GIX+F1 mice (10%) but not in the other strains. Severe glomerulonephritis and increased occurrence of lymphoproliferative lesions in these animals depend on the presence of GIX antigen. Besides genes controlling GIX antigen expression, other genes from both parental strains are required to create the basis in the progeny F1 mice for development of these diseases. Chronic production of GIX antibody may be necessary for development of severe glomerulonephritis and increased occurrence of lymphoproliferative diseases in GIX+F1 mice.