Lin28b controls a neonatal to adult switch in B cell positive selection

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 wildtype mice. We show that the heterochronic RNA-binding protein Lin28b potentiates a neonatal mode of B cell selection characterized by enhanced overall positive selection and the developmental progression of CD5+ immature B cells in particular. Importantly, Lin28b achieves this through 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 alters the rules for B cell selection during ontogeny through 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. BM cells from tet-Lin28b or WT mice fed DOX food for 2 weeks; or 3d old neonatal Lin28b wild-type, heterozygous or knockout mice