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

Stijn Vanhee, Hugo Åkerstrand, Trine Ahn Kristiansen, Sebak Datta, Giorgia Montano, Stefano Vergani, Stefan Lang, Jonas Ungerbäck, Alexander Doyle, Karin Olsson, Giulia Beneventi, Christina T. Jensen, Cristian Bellodi, Shamit Soneji, Mikael Sigvardsson, Elin Jaensson Gyllenbäck, Joan Yuan

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Abstract

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.

Original languageEnglish
Article numbereaax4453
JournalScience Immunology
Volume4
Issue number39
DOIs
Publication statusPublished - 2019

Subject classification (UKÄ)

  • Immunology in the medical area

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