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. F2 and backcross progeny from reciprocal F1 hybrids were classified for H-2 genotype and serum IgA levels and allowed to live out their lifespan. F2 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 X B10)F1 mothers, 693 compared with 540 days. The strain of the maternal parent also has been shown to affect the segregation of IgA phenotypes. An increased incidence of low IgA phenotype associated with H-2 genotype was observed among progeny of (B10.F X B10)F1 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 F1 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.