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

• Published in: PloS one 2011-04, Vol.6 (4), p.e18498-e18498
• Main Authors: Li, Suling, Symonds, Alistair L J, Zhu, Bo, Liu, Mengya, Raymond, Meera V, Miao, Tizong, Wang, Ping
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Autoimmune diseases; B cells; B-Lymphocytes - cytology; B-Lymphocytes - metabolism; Base Sequence; Biology; Bone marrow; Cadmium; CD4 antigen; CD8 antigen; Cell activation; Clonal selection; Defects; Dentistry; Developmental stages; DNA binding proteins; DNA Primers; Early Growth Response Protein 2 - genetics; Early Growth Response Protein 2 - physiology; EGR-1 protein; Egr-2 protein; Flow Cytometry; Gene expression; Genetic engineering; In Situ Nick-End Labeling; Lymphocytes; Lymphocytes B; Lymphocytes T; Maturation; Medicine; Mice; Mice, Transgenic; Natural killer cells; Notch1 protein; Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism; Pax5 protein; Positive selection; Proteins; Receptor, Notch1 - metabolism; Reduction; Rodents; Science; T cell receptors; T cells; T-Lymphocytes - cytology; T-Lymphocytes - metabolism; Thymocytes; Thymus; Thymus Gland - cytology; Thymus Gland - metabolism; Transcription factors; Transgenic animals; Transgenic mice
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0018498

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. 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. 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.