IL-7 mediates Ebf-1-dependent lineage restriction in early lymphoid progenitors

Blood. 2011 Aug 4;118(5):1283-90. doi: 10.1182/blood-2011-01-332189. Epub 2011 Jun 7.

Abstract

Deficiencies in the IL-7 signaling pathway result in severe disruptions of lymphoid development in adult mice. To understand more about how IL-7 deficiency impacts early lymphoid development, we have investigated lineage restriction events within the common lymphoid progenitor (CLP) compartment in IL-7 knockout mice. This revealed that although IL-7 deficiency had a minor impact on the development of LY6D(-) multipotent CLPs, the formation of the lineage restricted LY6D(+) CLP population was dramatically reduced. This was reflected in a low-level transcription of B-lineage genes as well as in a loss of functional B-cell commitment. The few Ly6D(+) CLPs developed in the absence of IL-7 displayed increased lineage plasticity and low expression of Ebf-1. Absence of Ebf-1 could be linked to increased plasticity because even though Ly6D(+) cells develop in Ebf-1-deficient mice, these cells retain both natural killer and dendritic cell potential. This reveals that IL-7 is essential for normal development of Ly6D(+) CLPs and that Ebf-1 is crucial for lineage restriction in early lymphoid progenitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / metabolism
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / physiology
  • Cell Differentiation / genetics
  • Cell Lineage / genetics*
  • Cells, Cultured
  • GPI-Linked Proteins / metabolism
  • Gene Expression Profiling
  • Interleukin-7 / genetics
  • Interleukin-7 / physiology*
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / physiology
  • Lymphoid Progenitor Cells / cytology
  • Lymphoid Progenitor Cells / metabolism
  • Lymphoid Progenitor Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microarray Analysis
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*

Substances

  • Antigens, Ly
  • Ebf1 protein, mouse
  • GPI-Linked Proteins
  • Interleukin-7
  • Ly6d protein, mouse
  • Trans-Activators