The natural history of spontaneous immunopathology and autoimmune phenomena was studied in hereditarily asplenic New Zealand Black x White F1 (NZB/W) hybrid mice. NZB/W mice, independent of sex, and including both Dh/+ and +/+ animals, had major age dependent reductions in immune function, including reduction in responsiveness to mitogens and sheep red blood cells and an inability to be tolerized by bovine gamma globulin. In contrast, there were major differences between male and female Dh/+ and +/+ mice with respect to survival and expression of renal disease. Dh/+ female mice had a lower median survival than +/+ mice; in contrast, male Dh/+ mice live longer than +/+ controls. These alterations in survival were reflected in renal and choroid plexus histology and proteinuria. The differences between female NZB/W Dh/+ and +/+ mice appeared to be accounted for by reductions in serum IgM, but enhanced IgG anti-DNA antibodies. The differences between female NZB/W Dh/+ and +/+ mice appeared secondary to the negligible titers of anti-nucleic acid antibodies in male Dh/+ animals. Hereditary absence of the spleen is significantly different from either neonatal or adult splenectomy, and its study, in parallel with other New Zealand immunologic mutants, suggests the existence of multiple independent developmental defects in the pathogenesis and clinical expression of autoimmune disease.
ASJC Scopus subject areas
- Developmental Biology