Successful differentiation to T cells, but unsuccessful B-cell generation, from B-cell-derived induced pluripotent stem cells

Int Immunol. 2011 Jan;23(1):65-74. doi: 10.1093/intimm/dxq458. Epub 2010 Dec 6.


Forced expression of certain transcription factors in somatic cells results in generation of induced pluripotent stem (iPS) cells, which differentiate into various cell types. We investigated T-cell and B-cell lineage differentiation from iPS cells in vitro. To evaluate the impact of iPS cell source, murine splenic B-cell-derived iPS (B-iPS) cells were generated after retroviral transduction of four transcription factors (Oct4, Sox2, Klf4 and c-Myc). B-iPS cells were identical to embryonic stem (ES) cells and mouse embryonic fibroblast (MEF)-derived iPS cells in morphology, ES cell marker expression as well as teratoma and chimera mouse formation. Both B-iPS and MEF-derived iPS cells differentiated into lymphocytes in OP9 co-culture systems. Both efficiently differentiated into T-cell lineage that produced IFN-γ on T-cell receptor stimulation. However, iPS cells including B-iPS cells were relatively resistant to B-cell lineage differentiation. One of the reasons of the failure of B-cell lineage differentiation seemed due to a defect of Pax5 expression in the differentiated cells. Therefore, current in vitro differentiation systems using iPS cells are sufficient for inducing T-cell but not B-cell lineage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Cell Differentiation / immunology*
  • Cell Line
  • Cell Lineage / genetics
  • Coculture Techniques
  • CpG Islands
  • DNA Methylation
  • Gene Expression
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / immunology
  • Kruppel-Like Factor 4
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, SCID
  • PAX5 Transcription Factor / genetics
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology


  • KLF4 protein, human
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • PAX5 Transcription Factor
  • PAX5 protein, human