Girls: Find a Mate Like Your Mother!?!

Abstract

In humans and other placental mammals, researchers have observed that a mother passes along some of her cells to her daughters in utero, and that these cells persist into adulthood. A new study in mice now shows how these cells can enhance the fitness of the daughter and her offspring [1]. It seems that the daughter develops immune tolerance to the antigens present in these cells—and if she mates with a male who has similar antigens, her fetus is shielded from destruction by the immune system. The evolution of the placenta was accompanied by the evolution of various systems to prevent the immune systems of the fetus and mother from destroying each other. Since the fetus inherits only half of its mother’s DNA, many maternal antigens are foreign to the fetus—yet immune cells of the fetus do not attack the mother. Tolerance to maternal antigens persists through adulthood and is observed even in mammals, such as rodents, that do not have fully developed immune systems until after birth. Jeremy Kinder and colleagues have uncovered a mechanism for this long-lived tolerance that involves regulatory T cells, cells that have an immune shielding effect. The researchers found that a mother’s cells prompt the development of antigen-specific regulatory T cells in a process that begins in utero. For a full regulatory T cell response to develop, the mother’s cells must persist through adulthood. The researchers found that daughters had more of their mother’s cells in their reproductive tracts than sons, and that the daughters also had a more robust regulatory T cell response to these cells. The regulatory T cells shielded the daughter’s fetuses from immune destruction—for instance, in experiments mimicking immune-mediated miscarriage—but this shielding effect occurred only if the fetus contained paternal antigens similar to the mother’s. The findings showcase a peculiar and previously unknown mechanism of inheritance that may provide a fitness advantage. The results also hint at a surprising upside to inbreeding.