| First Author | Vanhee S | Year | 2019 |
| Journal | Sci Immunol | Volume | 4 |
| Issue | 39 | PubMed ID | 31562190 |
| Mgi Jnum | J:293094 | Mgi Id | MGI:6435906 |
| Doi | 10.1126/sciimmunol.aax4453 | Citation | Vanhee S, et al. (2019) Lin28b controls a neonatal to adult switch in B cell positive selection. Sci Immunol 4(39) |
| abstractText | 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. |
