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EMBO Rep. 2017 Sep;18(9):1604-1617. doi: 10.15252/embr.201643735. Epub 2017 Jul 13.

The miR-15 family reinforces the transition from proliferation to differentiation in pre-B cells.

Author information

1
Division of Developmental Immunology, Biocenter, Medical University Innsbruck, Innsbruck, Austria.
2
Centre for Biological Signalling Studies (BIOSS), Albert-Ludwigs-University Freiburg, Freiburg, Germany.
3
Tyrolean Cancer Research Institute (TKFI), Innsbruck, Austria.
4
Division of Developmental Immunology, Biocenter, Medical University Innsbruck, Innsbruck, Austria Sebastian.herzog@i-med.ac.at.

Abstract

Precursor B lymphocytes expand upon expression of a pre-B cell receptor (pre-BCR), but then transit into a resting state in which immunoglobulin light chain gene recombination is initiated. This bi-phasic sequence is orchestrated by the IL-7 receptor (IL-7R) and pre-BCR signaling, respectively, but little is known about microRNAs fine-tuning these events. Here, we show that pre-B cells lacking miR-15 family functions exhibit prolonged proliferation due to aberrant expression of the target genes cyclin E1 and D3. As a consequence, they fail to trigger the transcriptional reprogramming normally accompanying their differentiation, resulting in a developmental block at the pre-B cell stage. Intriguingly, our data indicate that the miR-15 family is suppressed by both IL-7R and pre-BCR signaling, suggesting it is actively integrated into the regulatory circuits of developing B cells. These findings identify the miR-15 family as a novel element required to promote the switch from pre-B cell proliferation to differentiation.

KEYWORDS:

B Lymphocytes; lymphopoiesis; miR‐15; microRNA

PMID:
28705801
PMCID:
PMC5579393
DOI:
10.15252/embr.201643735
[Indexed for MEDLINE]
Free PMC Article

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