MiR-128-2 inhibits common lymphoid progenitors from developing into progenitor B cells

Oncotarget. 2016 Apr 5;7(14):17520-31. doi: 10.18632/oncotarget.8161.

Abstract

A considerable number of studies revealed that B cell development is finely regulated by transcription factors (TFs). Recent studies suggested that TFs are coordinated with microRNAs to control the development of B cells in numerous checkpoints. In the present study, we first found that miR-128-2 was differentially expressed in various immune organs and immunocytes. B cell development was inhibited in miR-128-2-overexpressed chimera and transgenic (TG) mice in bone marrow with decreased preproB, preB, proB, immature B, and recirculating B cells, as well as increased common lymphoid progenitors (CLPs). Further experiments showed that the apoptosis of CLP decreased, but proliferation was not altered in miR-128-2-overexpressed mice. Extensive studies suggested that the inhibition of apoptosis of CLP may be caused by miR-128-2 targeting A2B and MALT1, thereby increasing the phosphorylation of ERK and P38 MAPK. Such findings have prompted future investigations on the function of miR-128-2 in lymph genesis.

Keywords: B cell development; CLP; Immune response; Immunity; Immunology and Microbiology Section; apoptosis; miR-128-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Caspases / metabolism
  • Cell Differentiation / physiology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Lymphoid Progenitor Cells / cytology*
  • Lymphoid Progenitor Cells / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • MicroRNAs / immunology
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • Neoplasm Proteins / metabolism
  • Phosphorylation
  • Precursor Cells, B-Lymphoid / cytology*
  • Precursor Cells, B-Lymphoid / immunology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • MicroRNAs
  • Mirn128 microRNA, mouse
  • Neoplasm Proteins
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Caspases
  • Malt1 protein, mouse
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein