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Open Access Publications from the University of California

miRNAs Are Essential for the Regulation of the PI3K/AKT/FOXO Pathway and Receptor Editing during B Cell Maturation.

  • Author(s): Coffre, Maryaline;
  • Benhamou, David;
  • Rieß, David;
  • Blumenberg, Lili;
  • Snetkova, Valentina;
  • Hines, Marcus J;
  • Chakraborty, Tirtha;
  • Bajwa, Sofia;
  • Jensen, Kari;
  • Chong, Mark MW;
  • Getu, Lelise;
  • Silverman, Gregg J;
  • Blelloch, Robert;
  • Littman, Dan R;
  • Calado, Dinis;
  • Melamed, Doron;
  • Skok, Jane A;
  • Rajewsky, Klaus;
  • Koralov, Sergei B
  • et al.

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B cell development is a tightly regulated process dependent on sequential rearrangements of immunoglobulin loci that encode the antigen receptor. To elucidate the role of microRNAs (miRNAs) in the orchestration of B cell development, we ablated all miRNAs at the earliest stage of B cell development by conditionally targeting the enzymes critical for RNAi in early B cell precursors. Absence of any one of these enzymes led to a block at the pro- to pre-B cell transition due to increased apoptosis and a failure of pre-B cells to proliferate. Expression of a Bcl2 transgene allowed for partial rescue of B cell development, however, the majority of the rescued B cells had low surface immunoglobulin expression with evidence of ongoing light chain editing. Our analysis revealed that miRNAs are critical for the regulation of the PTEN-AKT-FOXO1 pathway that in turn controls Rag expression during B cell development.

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