DOI QR코드

DOI QR Code

Early Growth Response-1 Plays a Non-redundant Role in the Differentiation of B Cells into Plasma Cells

  • Oh, Yeon-Kyung (Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University) ;
  • Jang, Eunkyeong (Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University) ;
  • Paik, Doo-Jin (Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University) ;
  • Youn, Jeehee (Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University)
  • 투고 : 2015.04.03
  • 심사 : 2015.06.04
  • 발행 : 2015.06.30

초록

Early growth response (Egr)-1 is a $Cys_2-His_2-type$ zincfinger transcription factor. It has been shown to induce survival and proliferation of immature and mature B cells, respectively, but its role in the differentiation of B cells into plasma cells remains unclear. To examine the effects of Egr-1 deficiency on the activation of B cells, naive B cells from $Egr1^{-/-}$mice and their wild-type (WT) littermates were activated to proliferate and differentiate, and then assayed by FACS. Proportions of cells undergoing proliferation and apoptosis did not differ between $Egr1^{-/-}$ and WT mice. However, $Egr1^{-/-}$ B cells gave rise to fewer plasma cells than WT B cells. Consistently, $Egr1^{-/-}$ mice produced significantly lower titer of antigen-specific IgG than their WT littermates upon immunization. Our results demonstrate that Egr-1 participates in the differentiation program of B cells into plasma cells, while it is dispensable for the proliferation and survival of mature B cells.

키워드

참고문헌

  1. Tarlinton, D., A. Radbruch, F. Hiepe, and T. Dorner. 2008. Plasma cell differentiation and survival. Curr. Opin. Immunol. 20: 162-169. https://doi.org/10.1016/j.coi.2008.03.016
  2. Gomez-Martin, D., M. Diaz-Zamudio, M. Galindo-Campos, and J. Alcocer-Varela. 2010. Early growth response transcription factors and the modulation of immune response: implications towards autoimmunity. Autoimmun. Rev. 9: 454-458. https://doi.org/10.1016/j.autrev.2009.12.006
  3. Adamson, E., I. de Belle, S. Mittal, Y. Wang, J. Hayakawa, K. Korkmaz, D. O'Hagan, M. McClelland, and D. Mercola. 2003. Egr1 signaling in prostate cancer. Cancer Biol. Ther. 2: 617-622.
  4. Virolle, T., A. Krones-Herzig, V. Baron, G. De Gregorio, E. D. Adamson, and D. Mercola. 2003. Egr1 promotes growth and survival of prostate cancer cells. Identification of novel Egr1 target genes. J. Biol. Chem. 278: 11802-11810. https://doi.org/10.1074/jbc.M210279200
  5. Adamson, E. D., and D. Mercola. 2002. Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival. Tumour Biol. 23: 93-102. https://doi.org/10.1159/000059711
  6. McMahon, S. B., and J. G. Monroe. 1996. The role of early growth response gene 1 (egr-1) in regulation of the immune response. J. Leukoc. Biol. 60: 159-166. https://doi.org/10.1002/jlb.60.2.159
  7. Dinkel, A., K. Warnatz, B. Ledermann, A. Rolink, P. F. Zipfel, K. Burki, and H. Eibel. 1998. The transcription factor early growth response 1 (Egr-1) advances differentiation of pre-B and immature B cells. J. Exp. Med. 188: 2215-2224. https://doi.org/10.1084/jem.188.12.2215
  8. Gururajan, M., A. Simmons, T. Dasu, B. T. Spear, C. Calulot, D. A. Robertson, D. L. Wiest, J. G. Monroe, and S. Bondada. 2008. Early growth response genes regulate B cell development, proliferation, and immune response. J. Immunol. 181: 4590-4602. https://doi.org/10.4049/jimmunol.181.7.4590
  9. Seyfert, V. L., S. McMahon, W. Glenn, X. M. Cao, V. P. Sukhatme, and J. G. Monroe. 1990. Egr-1 expression in surface Ig-mediated B cell activation. Kinetics and association with protein kinase C activation. J. Immunol. 145: 3647-3653.
  10. Ke, J., M. Gururajan, A. Kumar, A. Simmons, L. Turcios, R. L. Chelvarajan, D. M. Cohen, D. L. Wiest, J. G. Monroe, and S. Bondada. 2006. The role of MAPKs in B cell receptor-induced down-regulation of Egr-1 in immature B lymphoma cells. J. Biol. Chem. 281: 39806-39818. https://doi.org/10.1074/jbc.M604671200
  11. Seyfert, V. L., S. B. McMahon, W. D. Glenn, A. J. Yellen, V. P. Sukhatme, X. M. Cao, and J. G. Monroe. 1990. Methylation of an immediate-early inducible gene as a mechanism for B cell tolerance induction. Science 250: 797-800. https://doi.org/10.1126/science.2237429
  12. Chen, L., S. Wang, Y. Zhou, X. Wu, I. Entin, J. Epstein, S. Yaccoby, W. Xiong, B. Barlogie, J. D. Shaughnessy, Jr., and F. Zhan. 2010. Identification of early growth response protein 1 (EGR-1) as a novel target for JUN-induced apoptosis in multiple myeloma. Blood 115: 61-70. https://doi.org/10.1182/blood-2009-03-210526
  13. Jang, E., W. S. Cho, M. L. Cho, H. J. Park, H. J. Oh, S. M. Kang, D. J. Paik, and J. Youn. 2011. $Foxp3^+$ regulatory T cells control humoral autoimmunity by suppressing the development of longlived plasma cells. J. Immunol. 186: 1546-1553. https://doi.org/10.4049/jimmunol.1002942
  14. Kim, S., K. Park, J. Choi, E. Jang, D. J. Paik, R. H. Seong, and J. Youn. 2015. $Foxp3^+$ regulatory T cells ensure B lymphopoiesis by inhibiting the granulopoietic activity of effector T cells in mouse bone marrow. Eur. J. Immunol. 45: 167-179. https://doi.org/10.1002/eji.201444532
  15. Segel, G. B., T. J. Woodlock, J. Xu, L. Li, R. E. Felgar, D. H. Ryan, M. A. Lichtman, and N. Wang. 2003. Early gene activation in chronic leukemic B lymphocytes induced toward a plasma cell phenotype. Blood Cells Mol. Dis. 30: 277-287. https://doi.org/10.1016/S1079-9796(03)00035-4
  16. Mora-Lopez, F., N. Pedreno-Horrillo, L. Delgado-Perez, J. A. Brieva, and A. Campos-Caro. 2008. Transcription of PRDM1, the master regulator for plasma cell differentiation, depends on an SP1/SP3/EGR-1 GC-box. Eur. J. Immunol. 38: 2316-2324. https://doi.org/10.1002/eji.200737861

피인용 문헌

  1. The progress of early growth response factor 1 and leukemia vol.5, pp.2, 2016, https://doi.org/10.5582/irdr.2015.01049
  2. Genome-Wide Identification of Target Genes for the Key B Cell Transcription Factor Ets1 vol.8, pp.None, 2017, https://doi.org/10.3389/fimmu.2017.00383
  3. Bach2 represses the AP-1-driven induction of interleukin-2 gene transcription in CD4+ T cells vol.50, pp.9, 2015, https://doi.org/10.5483/bmbrep.2017.50.9.124
  4. Transcriptional Analysis of the Human IgE-Expressing Plasma Cell Differentiation Pathway vol.10, pp.None, 2015, https://doi.org/10.3389/fimmu.2019.00402
  5. Iguratimod represses B cell terminal differentiation linked with the inhibition of PKC/EGR1 axis vol.21, pp.None, 2019, https://doi.org/10.1186/s13075-019-1874-2
  6. Diversity of Rainbow Trout Blood B Cells Revealed by Single Cell RNA Sequencing vol.10, pp.6, 2015, https://doi.org/10.3390/biology10060511