During development, haematopoietic stem and progenitor cells (HSPCs) experiencing high cellular stress produce increased levels of calreticulin, which triggers their engulfment by macrophages. A study now shows that repetitive elements promote the expression of β₂-microglobulin (B2M) in HSPCs to prevent their engulfment by macrophages.

Pessoa Rodrigues et al. performed a genome-wide screen in human cells and found that Toll-like receptor 3 (TLR3) regulated the expression of a ‘don’t eat-me’ signal, namely B2M. The authors then used zebrafish as a model and showed that depletion of tlr3 reduced the number of B2m⁺ HSPCs and enhanced HSPC engulfment by macrophages. B2m on HSPCs protected them from phagocytosis in the embryo and impacted HSPC clonality in adults. A series of analyses and functional experiments ultimately suggested a model in which endogenous repetitive elements in HSPCs trigger TLR3 signalling, which promotes the expression of B2M; then, in turn, B2M on the HSPC surface prevents HSPC phagocytosis by macrophages. Finally, the researchers presented evidence of potential conservation in mammals.

在发育过程中，经历高细胞应激的造血干细胞和祖细胞 （HSPC） 会产生更高水平的钙网蛋白，从而触发它们被巨噬细胞吞噬。现在的一项研究表明，重复元件促进 HSPC 中 β₂-微球蛋白 （B2M） 的表达，以防止它们被巨噬细胞吞噬。

Pessoa Rodrigues 等人在人类细胞中进行了全基因组筛选，发现 Toll 样受体 3 （TLR3） 调节“不吃我”信号的表达，即 B2M。然后，作者使用斑马鱼作为模型，表明 tlr3 的消耗减少了 B2m⁺ HSPC 的数量，并增强了巨噬细胞对 HSPC 的吞噬。HSPC 上的 B2m 保护它们免受胚胎中的吞噬作用，并影响成人的 HSPC 克隆性。一系列分析和功能实验最终提出了一个模型，其中 HSPC 中的内源性重复元件触发 TLR3 信号传导，从而促进 B2M 的表达;然后，反过来，HSPC 表面的 B2M 阻止 HSPC 被巨噬细胞吞噬。最后，研究人员提出了在哺乳动物中可能保护的证据。