Bcl11b Is Required for Differentiation and Survival of Alphabeta T Lymphocytes

Nat Immunol. 2003 Jun;4(6):533-9. doi: 10.1038/ni927. Epub 2003 Apr 28.

Abstract

The gene Bcl11b, which encodes zinc finger proteins, and its paralog, Bcl11a, are associated with immune-system malignancies. We have generated Bcl11b-deficient mice that show a block at the CD4-CD8- double-negative stage of thymocyte development without any impairment in cells of B- or gammadelta T cell lineages. The Bcl11b-/- thymocytes showed unsuccessful recombination of V(beta) to D(beta) and lacked the pre-T cell receptor (TCR) complex on the cell surface, owing to the absence of Tcrb mRNA expression. In addition, we saw profound apoptosis in the thymus of neonatal Bcl11b-/- mice. These results suggest that Bcl11b is a key regulator of both differentiation and survival during thymocyte development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / immunology
  • Cell Differentiation / immunology
  • Female
  • Hematopoietic Stem Cells / immunology
  • In Situ Nick-End Labeling
  • Lymphopoiesis / genetics
  • Lymphopoiesis / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, SCID
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Zinc Fingers / genetics
  • Zinc Fingers / immunology
  • ras Proteins / immunology*

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • Rit1 protein, mouse
  • ras Proteins