Early Growth Response Gene-2 (Egr-2) Regulates the Development of B and T Cells

Suling Li,Mengya Liu,Meera V Raymond,Tizong Miao,Ping Wang,Alistair L J Symonds,Bo Zhu,Ludovic Tailleux

doi:10.1371/journal.pone.0018498

Suling Li, Mengya Liu + Show 6 more

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https://doi.org/10.1371/journal.pone.0018498

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Abstract

BackgroundUnderstanding 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 FindingsThe 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.ConclusionsOur 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.

Highlights

T and B cell development in the thymus or bone marrow is a strictly controlled process that requires the precise alternation of gene expression programs orchestrated by specific transcription factors [1,2]
Our results demonstrate that Early Growth Response Gene-2 (Egr-2) expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells
We investigated the proximal signalling of T cell receptor and proliferation of thymocytes following stimulation with anti-CD3 in vitro and a similar result was found in thymocytes from wild type and Egr-2 cTg mice (Figure S2)

Summary

Introduction

T and B cell development in the thymus or bone marrow is a strictly controlled process that requires the precise alternation of gene expression programs orchestrated by specific transcription factors [1,2]. Mice deficient in Egr-1 or in Egr-2 have normal b-selection, but a defect in positive selection [6,10,13], while Egr-3 deficient thymocytes have a partial block at the DN3 stage that is largely due to defective proliferation of DN4 cells [7]. Mice lacking both Egr-1 and Egr-3 had a severe reduction of thymocyte numbers, with reduction of the DN4/DN3 ratio [14]. 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

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Results

Conclusion