Deletion of HO-1 blocks development of B lymphocytes in mice

Cell Signal. 2019 Nov:63:109378. doi: 10.1016/j.cellsig.2019.109378. Epub 2019 Jul 29.

Abstract

B lymphocytes, a key cluster of cells composing the immune system, can protect against abnormal biological factors. Heme oxygenase-1 (HO-1) plays important roles in cell proliferation and immune regulation, but its effects on the development and growth of B lymphocytes are still unknown. Herein, the count of B lymphocytes in HO-1 gene knockout (HO-1+/-) mice was significantly lower than that of the HO-1 gene wild-type (HO-1WT) mice. Meanwhile, the cell count of HO-1+/- mice did not recover after irradiation for one week, due to the G0/G1 phase arrest of Pro-B cells and the augmented apoptosis of Pre-B cells. Up-regulation of HO-1 by lentivirus attenuated the Pro-B cell cycle arrest and Pre-B cell apoptosis. To understand the molecular mechanism by which HO-1 knockout blocked B lymphocyte development, protein-to-protein interaction network and Western blot were used. The PI3K/AKT signaling pathway mediated the regulatory effects of HO-1 on B lymphocytes. In conclusion, HO-1 is a crucial transcriptional repressor for B cell development.

Keywords: B lymphocyte; Development; Gene knockout; Heme oxygenase-1; Mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle Checkpoints
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Gene Deletion
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Phosphatidylinositol 3-Kinases / metabolism
  • Precursor Cells, B-Lymphoid / cytology*

Substances

  • Membrane Proteins
  • Heme Oxygenase-1
  • Hmox1 protein, mouse