Cross-Generational Reproductive Fitness Enforced by Microchimeric Maternal Cells

Jeremy M. Kinder, Tony T. Jiang, James M. Ertelt, Lijun Xin, Beverly S. Strong, Aimen F. Shaaban, Sing Sing Way*

*Corresponding author for this work

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Exposure to maternal tissue during in utero development imprints tolerance to immunologically foreign non-inherited maternal antigens (NIMA) that persists into adulthood. The biological advantage of this tolerance, conserved across mammalian species, remains unclear. Here, we show maternal cells that establish microchimerism in female offspring during development promote systemic accumulation of immune suppressive regulatory T cells (Tregs) with NIMA specificity. NIMA-specific Tregs expand during pregnancies sired by males expressing alloantigens with overlapping NIMA specificity, thereby averting fetal wastage triggered by prenatal infection and non-infectious disruptions of fetal tolerance. Therefore, exposure to NIMA selectively enhances reproductive success in second-generation females carrying embryos with overlapping paternally inherited antigens. These findings demonstrate that genetic fitness, canonically thought to be restricted to Mendelian inheritance, is enhanced in female placental mammals through vertically transferred maternal cells that promote conservation of NIMA and enforce cross-generational reproductive benefits.

Original languageEnglish (US)
Pages (from-to)505-515
Number of pages11
JournalCell
Volume162
Issue number3
DOIs
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kinder, J. M., Jiang, T. T., Ertelt, J. M., Xin, L., Strong, B. S., Shaaban, A. F., & Way, S. S. (2015). Cross-Generational Reproductive Fitness Enforced by Microchimeric Maternal Cells. Cell, 162(3), 505-515. https://doi.org/10.1016/j.cell.2015.07.006