Early growth response gene-2 (Egr-2) regulates the development of B and T cells

PLoS One. 2011 Apr 14;6(4):e18498. doi: 10.1371/journal.pone.0018498.

Abstract

Background: Understanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development.

Methods and findings: The expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2(+) lymphocytes resulted in a severe reduction of CD4(+)CD8(+) (DP) cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP) T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow.

Conclusions: Our results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism
  • Base Sequence
  • DNA Primers
  • Early Growth Response Protein 2 / genetics
  • Early Growth Response Protein 2 / physiology*
  • Flow Cytometry
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Transgenic
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism
  • Receptor, Notch1 / metabolism
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / metabolism

Substances

  • DNA Primers
  • Early Growth Response Protein 2
  • Egr2 protein, mouse
  • Notch1 protein, mouse
  • Nr4a1 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Receptor, Notch1