ROS CALR and TLR3 B2m signaling balance eat me and do not eat me signals for HSC quality assurance by macrophages

Macrophage quality assures normal blood stem cells use one of these eat me signals that isimportant to determine the number of hematopoietic clones that participate in adult hematopoiesis.Macrophages either engulf a stem cell completely (referred to as dooming) or capture portions of thestem cell cellular material (referred to as grooming). In the latter case, the stem cell continues to divide.This interaction is mediated by a signal called calreticulin (Calr) on the surface of hematopoietic stem andprogenitor cells (HSPCs), known as an eat-me signal. Surface Calr levels are increased in stem cells withhigher levels of reactive oxygen species (ROS), but the specific molecular cues that regulate the doomingversus grooming behavior are still unknown. We found that b2 microglobulin (B2m) is a do not eat-memolecule and show that both Calr and B2m must balance the eat me and do not eat me cues to qualityassure hematopoietic stem cells.