LAUSR

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.