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Lin28b controls a neonatal to adult switch in B cell positive selection
Lund Univ, Sweden.
Lund Univ, Sweden.
Lund Univ, Sweden.
Lund Univ, Sweden.
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2019 (English)In: SCIENCE IMMUNOLOGY, ISSN 2470-9468, Vol. 4, no 39, article id eaax4453Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE , 2019. Vol. 4, no 39, article id eaax4453
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-161412DOI: 10.1126/sciimmunol.aax4453ISI: 000491059700003PubMedID: 31562190OAI: oai:DiVA.org:liu-161412DiVA, id: diva2:1367045
Note

Funding Agencies|European Research CouncilEuropean Research Council (ERC) [715313]; Wallenberg Academy Fellows; Swedish Research CouncilSwedish Research Council; StemTherapy; Wenner-Gren Foundation; Swedish Cancer SocietySwedish Cancer Society; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation

Available from: 2019-10-31 Created: 2019-10-31 Last updated: 2019-10-31

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Sigvardsson, Mikael
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Division of Hematopoiesis and Developmental BiologyFaculty of Medicine and Health Sciences
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CiteExportLink to record
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Citation style
  • apa
  • ieee
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More styles
Language
  • de-DE
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  • Other locale
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Output format
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