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

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T1 - Lin28b controls a neonatal to adult switch in B cell positive selection

AU - Vanhee, Stijn

AU - Åkerstrand, Hugo

AU - Kristiansen, Trine Ahn

AU - Datta, Sebak

AU - Montano, Giorgia

AU - Vergani, Stefano

AU - Lang, Stefan

AU - Ungerbäck, Jonas

AU - Doyle, Alexander

AU - Olsson, Karin

AU - Beneventi, Giulia

AU - Jensen, Christina T.

AU - Bellodi, Cristian

AU - Soneji, Shamit

AU - Sigvardsson, Mikael

AU - Gyllenbäck, Elin Jaensson

AU - Yuan, Joan

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1126/sciimmunol.aax4453

DO - 10.1126/sciimmunol.aax4453

M3 - Article

C2 - 31562190

AN - SCOPUS:85072704797

VL - 4

JO - Science Immunology

JF - Science Immunology

SN - 2470-9468

IS - 39

M1 - eaax4453

ER -