B Cell Homeostasis Under Control Of microRNAs

Development of B lineage cells is guided by antigen receptor signaling through positive and negative selection check-points. The PI3K has been shown as the major pathway in regulating positive and negative selection of developing B cells, and survival of mature B cells. Activation of PI3K is balanced by phosphatase and tensin homolog (Pten), the PI3K’s main antagonistic phosphatase. Yet, the extent of feedback regulation between PI3K activity and Pten expression during B cell development is unclear. We study the regulation of PI3K by microRNAs and uncovered an autostimulatory axis composed of a transcription factor (c-Myc), a microRNA (miR17-92) and Pten. The mechanism by which this biochemical circuit controls PI3K activity and determines B cell fate decisions in developmental check-points will be discussed,