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The miR‐15 family reinforces the transition from proliferation to differentiation in pre‐B cells
Author(s) -
Lindner Silke E,
Lohmüller Michael,
Kotkamp Bianka,
Schuler Fabian,
Knust Zeynep,
Villunger Andreas,
Herzog Sebastian
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201643735
Subject(s) - library science , biology , computer science
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 micro RNA s 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.