Grandmaternal cells in cord blood

Abstract

Background: During pregnancy a feto-maternal exchange of cells through the placenta conducts to maternal microchimerism (Mc) in the child and fetal Mc in the mother. Because of this bidirectional traffic of cells, pregnant women have also acquired maternal cells in utero from their mother and could transfer grandmaternal (GdM) cells to their child through the maternal bloodstream during pregnancy. Thus, cord blood (CB) samples could theoretically carry GdMMc. Nevertheless this has never been demonstrated. Methods: Using Human Leukocyte Antigen (HLA)-specific quantitative PCR assays on three-generation families, we were able to test 28 CB samples from healthy primigravid women for GdMMc in whole blood (WB) and isolated cells (PBMC, T, B, granulocytes, stem cells). Findings: Five CB samples (18%) had GdMMc which could not be confounded with maternal source, with quantities 100 fold lower than maternal Mc in WB and PBMC. Risk of aneuploidies and/or related invasive prenatal procedures significantly correlated with the presence of GdMMc in CB (p=0.024). Significantly decreased HLA compatibility was observed in three-generation families from CB samples carrying GdMMc (p=0.019). Interpretation: Transgenerational transfer of cells could have implications in immunology and evolution. Further analyses will be necessary to evaluate whether GdMMc in CB is a passive or immunologically active transfer and whether invasive prenatal procedures could trigger GdMMc.

Reproductive outcomes after pregnancy-induced displacement of preexisting microchimeric cells

“…Additional outstanding questions remain regarding why the repertoire of exceptionally rare microchimeric cells is not expandable, especially considering their numerical and cellular interindividual variability during embryonic development ( 38 , 39 ) and protective role against early life infection ( 40 ). Given increased circulating MMc levels in women during pregnancy ( 41 ) and recent identification of grandmaternal microchimeric cells in first-pregnancy specimens from cord blood ( 42 ), purposeful MMc displacement to further extend tolerance to grandchildren represents a provocative explanation that requires further evaluation. Collectively, these results regarding how pregnancy affects the outcomes of future pregnancies in mothers and their daughters reveal distinctions in how familial antigens are immunologically remembered and how tolerance to fetal alloantigens is naturally optimized to improve pregnancy outcomes.…”

Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing

“…1 ) in detecting GFP +/− maternal cells. Furthermore, to prevent detection of GFP-positive grand-maternal cells 39 , the mother mice were obtained by crossing BALB/cByJJcl wild-type female mice with GFP -homozygous male mice. MHC types of mice were carefully designed for utility to concentrate MMc cells using magnetic cell sorting system (Fig.…”

Age is just a number: long‐lasting T‐cell immunity can span several lifetimes

“…Coincidentally, a naturally occurring human model for transgenerational (T) cells also exists, whereby cells are passed from mother to child during pregnancy and have been shown to survive in the offspring for extended periods 7 . Some studies even suggest that grandmaternal cells can be found in umbilical cord blood of second‐generation offspring 8 . A point of debate regarding the purpose of these long‐lived cells has always been the matter of location.…”

“…7 Some studies even suggest that grandmaternal cells can be found in umbilical cord blood of secondgeneration offspring. 8 A point of debate regarding the purpose of these long-lived cells has always been the matter of location. Why would these cells circulate systemically instead of homing to their target tissue?…”