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

Vanhee, Stijn LU ; Åkerstrand, Hugo LU ; Kristiansen, Trine Ahn LU ; Datta, Sebak LU ; Montano, Giorgia LU ; Vergani, Stefano LU ; Lang, Stefan LU orcid ; Ungerbäck, Jonas LU ; Doyle, Alexander LU and Olsson, Karin LU , et al. (2019) In Science Immunology 4(39).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Immunology
volume
4
issue
39
article number
eaax4453
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85072704797
  • pmid:31562190
ISSN
2470-9468
DOI
10.1126/sciimmunol.aax4453
language
English
LU publication?
yes
id
84cebe50-9053-4cc2-ba20-5fd4e1b595e4
date added to LUP
2019-10-10 09:47:45
date last changed
2024-04-30 22:50:09
@article{84cebe50-9053-4cc2-ba20-5fd4e1b595e4,
  abstract     = {{<p>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.</p>}},
  author       = {{Vanhee, Stijn and Åkerstrand, Hugo and Kristiansen, Trine Ahn and Datta, Sebak and Montano, Giorgia and Vergani, Stefano and Lang, Stefan and Ungerbäck, Jonas and Doyle, Alexander and Olsson, Karin and Beneventi, Giulia and Jensen, Christina T. and Bellodi, Cristian and Soneji, Shamit and Sigvardsson, Mikael and Gyllenbäck, Elin Jaensson and Yuan, Joan}},
  issn         = {{2470-9468}},
  language     = {{eng}},
  number       = {{39}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Immunology}},
  title        = {{Lin28b controls a neonatal to adult switch in B cell positive selection}},
  url          = {{https://lup.lub.lu.se/search/files/80468618/SV_revision_fin_merge.pdf}},
  doi          = {{10.1126/sciimmunol.aax4453}},
  volume       = {{4}},
  year         = {{2019}},
}