The opposing roles of the transcription factor E2A and its antagonist Id3 that orchestrate and enforce the naive fate of T cells

Nat Immunol. 2011 Aug 21;12(10):992-1001. doi: 10.1038/ni.2086.

Abstract

It is established that the transcription factor E2A and its antagonist Id3 modulate the checkpoints consisting of the precursor to the T cell antigen receptor (pre-TCR) and the TCR. Here we demonstrate that Id3 expression was higher beyond the pre-TCR checkpoint, remained high in naive T cells and showed a bimodal pattern in the effector-memory population. We show how E2A promoted T lineage specification and how pre-TCR-mediated signaling affected E2A genome-wide occupancy. Thymi in Id3-deficient mice had aberrant development of effector-memory cells, higher expression of the chemokine receptor CXCR5 and the transcriptional repressor Bcl-6 and, unexpectedly, T cell-B cell conjugates and B cell follicles. Collectively, our data show how E2A acted globally to orchestrate development into the T lineage and that Id3 antagonized E2A activity beyond the pre-TCR checkpoint to enforce the naive fate of T cells.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Immunologic Memory
  • Immunophenotyping
  • Inhibitor of Differentiation Proteins / physiology*
  • Leukocyte Common Antigens / analysis
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, CXCR5 / analysis
  • Spleen / immunology
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • CXCR5 protein, mouse
  • Inhibitor of Differentiation Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, CXCR5
  • Tcf3 protein, mouse
  • Idb3 protein, mouse
  • Leukocyte Common Antigens