The ability of B-1 cells to become positively selected into the mature B cell pool, despite being weakly self-reactive, has puzzled the field since its initial discovery. Here, we explore changes in B cell positive selection as a function of developmental time by exploiting a link between CD5 surface levels and the natural occurrence of self-reactive B cell receptors (BCRs) in BCR wild-type mice. We show that the heterochronic RNA binding protein Lin28b potentiates a neonatal mode of B cell selection characterized by enhanced overall positive selection in general and the developmental progression of CD5⁺ immature B cells in particular. Lin28b achieves this by amplifying the CD19/PI3K/c-Myc positive feedback loop, and ectopic Lin28b expression restores both positive selection and mature B cell numbers in CD19^−/− adult mice. Thus, the temporally restricted expression of Lin28b relaxes the rules for B cell selection during ontogeny by modulating tonic signaling. We propose that this neonatal mode of B cell selection represents a cell-intrinsic cue to accelerate the de novo establishment of the adaptive immune system and incorporate a layer of natural antibody-mediated immunity throughout life.

自最初发现以来，尽管B-1细胞的自我反应能力较弱，但其被积极选择进入成熟B细胞库的能力却困扰着该领域。在这里，我们通过利用CD5表面水平与BCR野生型小鼠中自然发生的自我反应性B细胞受体（BCR）之间的联系，探索B细胞阳性选择随发育时间的变化。我们显示，异时RNA结合蛋白Lin28b增强了B细胞选择的新生儿模式，其特征是总体上增强了总体阳性选择，尤其是CD5 ⁺未成熟B细胞的发育进程。Lin28b通过扩增CD19 / PI3K / c-Myc阳性反馈环来实现这一目标，而异位Lin28b表达可恢复CD19中的阳性选择和成熟B细胞数量^-/-成年小鼠。因此，Lin28b的时间受限制的表达通过调节强直性信号传导放松了个体发育过程中B细胞选择的规则。我们建议，这种B细胞选择的新生儿模式代表了一种细胞内在的提示，以加速从头建立适应性免疫系统，并在整个生命过程中整合一层天然抗体介导的免疫力。