Microchimeric Maternal Cells Promote Reproductive Fitness Across Generations

Published Online July 23, 2015
Cell

The long-standing scientific mystery of how the developing fetus avoids rejection by their mother’s immune cells remains unresolved. However, new clues are emerging.

A research team led by Sing Sing Way, MD, PhD, Division of Infectious Diseases, reports the bidirectional exchange and persistence of maternal cells in offspring, and offspring cells in mothers during pregnancy, may help unlock the mystery of how pregnancy naturally works.

Genetically foreign maternal cells promote in offspring a systemic accumulation of immune-suppressive regulatory T cells. These cells are specific to non-inherited maternal antigens (NIMA), the team reports.

Exposure to NIMA enhances the odds of successful pregnancy when a woman encounters a partner with similar genetic traits as her own mother. This process, common to all placental mammals, helps protect against pregnancy complications often triggered by prenatal infection.

“Our research proves one aspect of nature’s intent in this intricately orchestrated transfer of cells during fetal development,” Way says.

These microchimeric cells are very rare, ranging from one in 100,000 to one in one million offspring cells. Humans are comprised of more than 30 trillion cells. That means each may contain up to 300 million of our mother’s cells.

“It was just miraculous to us that these cells could persist despite being genetically and immunological foreign,” says first author Jeremy Kinder, a graduate student in Way’s lab. “When we looked at them quantitatively, we saw that they’re able to mediate reproductive benefits.”

Understanding how these cells work could help prevent preterm births, treat certain autoimmune disorders, or help avoid transplant tissue rejection.

“We’re letting these cells teach us fundamental immunology,” Way says, “because they have learned some tricks that we didn’t appreciate before. But clearly nature has figured it out.”