Autoimmunity in aged mice. Occurrence of autoagglutinating factors in the blood of aged mice with medium and long life-spans

Abstract

Studies of mice with medium and long life-spans were undertaken to determine whether the autoantibodies that occur in disease and in aging are due to a common underlying cause or to separate mechanisms. Results were obtained using untreated and trypsinized syngeneic red blood cells (RBC) to detect anti-RBC autoantibodies in the plasma of aged mice. The occurrence of these autoantibodies in mice appears to be independent of strain, average life-span, and rearing conditions and their appearance in mice free of autoimmune diseases suggests that they are not associated exclusively with such diseases. However, the frequency of mice with autoantibodies increases with advancing age and tends to be higher in females. These autoantibodies are distinct from natural heteroantibodies, but they are reactive against RBC from other mouse strains. Their activity is temperature sensitive, to the extent that they are more reactive at 22°C than at 37°C. Their striking affinity for trypsinized RBC suggests that their activity may be against inaccessible, nonpeptidic determinants, most likely of carbohydrate moiety. The autoantibodies are primarily IgM immunoglobulins, and in some cases they can be IgA immunoglobulins. RBC from young and old mice show the same immunogenic potential, so changes in the RBC due to somatic variations are unlikely to be the cause for their origin. The possible origin and significance of these autoantibodies are discussed in the light of current evidence.