The immunological intrigue of microchimerism: tracing fetal and maternal cells throughout the body

Microchimerism is an intriguing phenomenon, where cells of fetal origin establish themselves as temporary or permanent colonies in maternal tissues and vice versa. The presence of fetal cells in maternal tissues has been linked to beneficial and detrimental health outcomes in several auto-immune diseases. Fetal cells are speculated to trigger allo-autoimmune responses in maternal tissues, though it remains inconclusive whether fetal cells causally contribute to disease origin or progression. Despite decades of study, many fundamental aspects of microchimerism —the origin of the cells, their function, their ability to evade the immune system, and their frequency throughout the body— remain unresolved. This is primarily due to methodological limitations, such as the lack of good models to study these cells and the lack of efficient, sensitive detection techniques. Here, we describe a highly sensitive way to accurately and absolutely quantify the presence of both fetal and maternal microchimeric cells by using digital droplet PCR. The technique is applied to a transgenic animal model to detect the endogenous fluorescent signal of either fetal or maternal cells against non-fluorescent host tissues. We adopt a whole-body approach across different timepoints during and after gestation and focus on immunological similarity between mother and offspring, by comparing syngeneic versus allogeneic gestation, as well as examining differences in parameters such as litter size and fetal sex. This project sets a foundation for future work uncovering the characteristics, and potential biological functions of fetal and maternal microchimeric cells.