Transcriptional control of early T and B cell developmental choices

Annu Rev Immunol. 2014;32:283-321. doi: 10.1146/annurev-immunol-032712-100024. Epub 2014 Jan 22.

Abstract

T and B cells share a common somatic gene rearrangement mechanism for assembling the genes that code for their antigen receptors; they also have developmental pathways with many parallels. Shared usage of basic helix-loop-helix E proteins as transcriptional drivers underlies these common features. However, the transcription factor networks in which these E proteins are embedded are different both in membership and in architecture for T and B cell gene regulatory programs. These differences permit lineage commitment decisions to be made in different hierarchical orders. Furthermore, in contrast to B cell gene networks, the T cell gene network architecture for effector differentiation is sufficiently modular so that E protein inputs can be removed. Complete T cell-like effector differentiation can proceed without T cell receptor rearrangement or selection when E proteins are neutralized, yielding natural killer and other innate lymphoid cells.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation / genetics*
  • Cell Differentiation / immunology
  • Cell Lineage
  • Gene Expression Regulation, Developmental
  • Humans
  • Lymphoid Progenitor Cells / cytology
  • Lymphoid Progenitor Cells / metabolism
  • Lymphopoiesis / physiology
  • Phenotype
  • Receptors, Notch / metabolism
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism*
  • Transcription, Genetic*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Receptors, Notch