IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte β-selection

Nat Immunol. 2015 Apr;16(4):397-405. doi: 10.1038/ni.3122. Epub 2015 Mar 2.


Signaling via the pre-T cell antigen receptor (pre-TCR) and the receptor Notch1 induces transient self-renewal (β-selection) of TCRβ(+) CD4(-)CD8(-) double-negative stage 3 (DN3) and DN4 progenitor cells that differentiate into CD4(+)CD8(+) double-positive (DP) thymocytes, which then rearrange the locus encoding the TCR α-chain (Tcra). Interleukin 7 (IL-7) promotes the survival of TCRβ(-) DN thymocytes by inducing expression of the pro-survival molecule Bcl-2, but the functions of IL-7 during β-selection have remained unclear. Here we found that IL-7 signaled TCRβ(+) DN3 and DN4 thymocytes to upregulate genes encoding molecules involved in cell growth and repressed the gene encoding the transcriptional repressor Bcl-6. Accordingly, IL-7-deficient DN4 cells lacked trophic receptors and did not proliferate but rearranged Tcra prematurely and differentiated rapidly. Deletion of Bcl6 partially restored the self-renewal of DN4 cells in the absence of IL-7, but overexpression of BCL2 did not. Thus, IL-7 critically acts cooperatively with signaling via the pre-TCR and Notch1 to coordinate proliferation, differentiation and Tcra recombination during β-selection.

Publication types

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

MeSH terms

  • Animals
  • CD4 Antigens / genetics
  • CD4 Antigens / immunology
  • CD8 Antigens / genetics
  • CD8 Antigens / immunology
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Gene Expression Regulation
  • Interleukin-7 / deficiency
  • Interleukin-7 / genetics*
  • Interleukin-7 / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / immunology
  • Proto-Oncogene Proteins c-bcl-6 / deficiency
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / immunology
  • Receptor, Notch1 / genetics*
  • Receptor, Notch1 / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Recombination, Genetic
  • Signal Transduction
  • Thymocytes / cytology
  • Thymocytes / immunology
  • Thymocytes / metabolism*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism


  • CD4 Antigens
  • CD8 Antigens
  • Interleukin-7
  • Notch1 protein, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • Receptor, Notch1
  • Receptors, Antigen, T-Cell, alpha-beta
  • interleukin-7, mouse
  • Bcl2 protein, mouse

Associated data

  • GEO/GSE63932