Abstract
Systemic lupus erythematosus (SLE) is a complex autoimmune disease that has a strong preference for women of child-bearing age. Maternal factors play an essential role in shaping the immune system of the newborn, yet it is unknown whether maternal factors could modulate the development of SLE in the offspring. Activation-induced cytidine deaminase (AID) is an enzyme required for somatic hypermutation and class switch recombination. Given that IgG and IgA isotypes account for the vast majority of passive immunity in rodents, our previously established AID-deficient BXSB mice provide a model in which maternal antibodies that can be transferred to the offspring are greatly diminished and have restricted repertoire. In this study, we compared genotypically identical mice born to either AID-sufficient dams or AID-deficient dams and evaluated the effects of maternal antibodies in disease progression. Offspring from knockout dams developed disease at a faster rate, as shown by more severe nephritis and elevated pathogenic autoantibodies compared to their counterparts born to wild-type dams. When immune competent pups were cross fostered onto AID-deficient dams, these mice exhibited more severe disease characteristics, including exacerbated lupus nephritis, increased levels of circulating antinuclear antibodies, and more activated T cells. These results suggest that a protective antibody effect contributes to the modulation of SLE progression in postnatal period. Overall, these findings highlight the importance of maternal antibodies in programming the immune system and altering SLE development in offspring.
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