Interaction of H-2 genotype and basal serum immunoglobulin a level influences longevity

The congenic pair of mice, C57BL/10 (B10) and C57BL/10.F (B10.F), differ at the H-2 locus and have mean ages at death of 706 and 456 days, respectively. B10.F also has reduced basal serum IgA levels compared with B10, 63 and 256 mg/dl, respectively. Controlled matings between the two strains of mice were used to identify genetic factors that govern longevity. F 2 and backcross progeny from reciprocal F 1 hybrids were classified for H-2 genotype and serum IgA levels and allowed to live out their lifespan. F 2 and backcross progeny homozygous for the H-2 allele of B10.F had a mean age at death (602 days) significantly reduced from that of progeny homozygous for the H-2 allele of B10 (689 days). However, the greatest reduction of lifespan occurred among progeny of the (B10.F × B10)F 1 mothers. Survival curves demonstrated a relationship between low serum IgA levels and shortened lifespan and no maternal effect was observed. The basis of the shortened lifespan among progeny of F 1 hybrids in which the maternal parent was B10.F was the increased incidence of offspring with low IgA phenotypes. The apparent association of H-2 and shortened lifespan also was because the low IgA phenotype was more frequent among progeny that carried the H-2 allele of the B10.F strain. The B10.F mice spontaneously shed an endogenous ecotropic retrovirus which may be responsible for the maternal effect on immunoglobulin levels and lifespan.