The autoimmune checkpoint during B cell maturation eliminates self‐antigen reactive specificities from the mature B cell repertoire. However, an exception to this rule is illustrated by B‐1 cells, an innate‐like self‐reactive B cell subset that is positively selected into the mature B cell pool in a self‐antigen‐driven fashion. The mechanisms by which B‐1 cells escape central tolerance have puzzled the field for decades. A key clue comes from their restricted developmental window during fetal and neonatal life. Here we use B‐1 cells as a prototypic early life derived B cell subset to explore developmental changes in the constraints of B cell selection. We discuss recent advancements in the understanding of the molecular program, centered around the RNA binding protein Lin28b, that licenses self‐reactive B‐1 cell output during ontogeny. Finally, we speculate on the possible link between the unique rules of early life B cell tolerance and the establishment of B cell – microbial mutualism to propose an integrated model for how developmental and environmental cues come together to create a protective layer of B cell memory involved in neonatal immune imprinting.

中文翻译：

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B细胞选择规则的发展变化

B 细胞成熟过程中的自身免疫检查点消除了成熟 B 细胞库中的自身抗原反应特异性。然而，B-1 细胞说明了这条规则的一个例外，B-1 细胞是一种先天样的自反应 B 细胞亚群，它以自身抗原驱动的方式被积极地选入成熟 B 细胞库。几十年来，B-1 细胞逃避中枢耐受的机制一直困扰着该领域。一个关键的线索来自他们在胎儿和新生儿生命期间受限的发育窗口。在这里，我们使用 B-1 细胞作为原型早期生命衍生的 B 细胞亚群，以探索 B 细胞选择限制的发育变化。我们讨论了以 RNA 结合蛋白 Lin28b 为中心的分子程序理解的最新进展，该程序允许个体发育过程中的自我反应性 B-1 细胞输出。最后，