Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes

Nat Immunol. 2018 Mar;19(3):279-290. doi: 10.1038/s41590-018-0046-x. Epub 2018 Feb 12.


Deletion of master regulators of the B cell lineage reprograms B cells into T cells. Here we found that the transcription factor Hoxb5, which is expressed in uncommitted hematopoietic progenitor cells but is not present in cells committed to the B cell or T cell lineage, was able to reprogram pro-pre-B cells into functional early T cell lineage progenitors. This reprogramming started in the bone marrow and was completed in the thymus and gave rise to T lymphocytes with transcriptomes, hierarchical differentiation, tissue distribution and immunological functions that closely resembled those of their natural counterparts. Hoxb5 repressed B cell 'master genes', activated regulators of T cells and regulated crucial chromatin modifiers in pro-pre-B cells and ultimately drove the B cell fate-to-T cell fate conversion. Our results provide a de novo paradigm for the generation of functional T cells through reprogramming in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • Cell Differentiation
  • Cell Lineage / genetics
  • Cell Lineage / immunology*
  • Cellular Reprogramming / genetics
  • Cellular Reprogramming / immunology*
  • Homeodomain Proteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, SCID
  • Precursor Cells, B-Lymphoid / cytology
  • T-Lymphocytes / cytology*


  • Homeodomain Proteins
  • Hoxb5 protein, mouse