Stage-specific functions of E-proteins at the β-selection and T-cell receptor checkpoints during thymocyte development

Immunol Res. 2011 Apr;49(1-3):202-15. doi: 10.1007/s12026-010-8182-x.

Abstract

The E-protein transcription factors E2A and HEB function in a lineage- and stage-specific manner to orchestrate many critical events throughout lymphocyte development. The function of E-proteins in both B- and T-lymphocyte development has been extensively studied through the use of single-gene knockout animals. Unlike B cells, which rely primarily on E2A alone, T cells are regulated by the combinatorial expression of both E2A and HEB. Therefore, many of the roles of E-proteins during T-cell development may be masked in single-gene knockout studies due to the compensatory function of E2A and HEB. More recently, our laboratory has established double-conditional knockout models to eliminate both E2A and HEB in a stage-specific manner throughout T-cell development. These models, in combination with other complimentary genetic approaches, have identified new E-protein functions at each of the two major T-cell developmental checkpoints. Here, we will discuss how E-proteins function to regulate the expression of T-cell receptor components and cell cycle at the β-selection checkpoint, and how they control positive selection, survival, and lineage-specific gene expression at the subsequent T-cell receptor checkpoint.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity
  • Animals
  • B-Lymphocytes / immunology
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Cycle / genetics
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Hyaluronan Receptors / genetics
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Mice
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hyaluronan Receptors
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Antigen, T-Cell
  • Tcf12 protein, mouse
  • Tcf3 protein, mouse