miR‐221 redirects precursor B cells to the BM and regulates their residence

Abstract

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MiR221 promotes precursor B‐cell retention in the bone marrow by amplifying the PI3K‐signaling pathway in mice

“…These experiments confirm our findings, that miR221‐enhanced PI3Kinase functions mediate in vivo retention of preBI‐cells in BM. Similar to termination of miR221‐expression the inhibition of PI3Kinase terminates preBI‐cell retention in BM in vivo, thereby not enhancing differentiation. Ectopic PTEN expression, devoid of miR221 binding sites, should complement and abolish the PI3K activation effect, caused by miR221 downregulation of endogenous and miR221‐sensitive PTEN.…”

“…PAX5‐deficient pro‐preB‐cells could be induced in vitro, in the appropriate tissue culture conditions, to differentiate multiple hematopoietic lineages, except to B‐cells . Important for the studies presented here is, that PAX5‐deficient preB‐cells were found to express high levels of miR221, like other hematopoietic progenitor cells including HSCs, while normal preBI‐cells expressed very low levels of miR221 .…”

“…They are involved in the regulation of cellular processes like apoptosis, proliferation, lineage commitment, and differentiation in the hematopoietic system, including B‐cell development . We previously investigated the possible role of miR221 expression during the phase of differentiation from pro‐preB‐cells to preBI‐cells by re‐expressing miR221 in normally low‐expressing preBI‐cells . Interestingly, the expression of miR221 in preBI cells renews their capability to home into the BM, reside there, and establish a pool of preBI‐cells.…”

MicroRNAs as master regulators of immune responses in transplant recipients

“…Another miRNA, miR146a, controls the expression of Irak1 and Traf6 in splenic B cells and has been implicated in B1 cell development [32,33]. miR-221 plays a role in the retention of the early B lineage cells in bone marrow [34]. miR-155 plays an important role in both germinal center B cells and B cell memory responses [35,36] and regulates a transcription factor PU.…”

MicroRNAs, Major Players in B Cells Homeostasis and Function

“…Starting from the fact that PAX5 (paired box 5) participate in B-cell fate, Knoll et al have shown the down-regulation of miR-221 and miR-222 during B-lymphocyte development, and the involvement of miR-221 in the retention of early B-lineage cells in bone marrow (29). A similar procedure has been shown with the transcription factor PU.1 {encoded by the Sfpi1 gene [SPI1 spleen focus forming virus (SFFV) proviral integration oncogene]}, because high ectopic expression of Pu.1 in multipotent progenitors promotes myeloid cell development at the expense of B-cell development (6).…”