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Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein.

Publication ,  Journal Article
Lee, CH; Melchers, M; Wang, H; Torrey, TA; Slota, R; Qi, C-F; Kim, JY; Lugar, P; Kong, HJ; Farrington, L; van der Zouwen, B; Zhou, JX ...
Published in: J Exp Med
January 23, 2006

Interferon (IFN) consensus sequence-binding protein/IFN regulatory factor 8 (IRF8) is a transcription factor that regulates the differentiation and function of macrophages, granulocytes, and dendritic cells through activation or repression of target genes. Although IRF8 is also expressed in lymphocytes, its roles in B cell and T cell maturation or function are ill defined, and few transcriptional targets are known. Gene expression profiling of human tonsillar B cells and mouse B cell lymphomas showed that IRF8 transcripts were expressed at highest levels in centroblasts, either from secondary lymphoid tissue or transformed cells. In addition, staining for IRF8 was most intense in tonsillar germinal center (GC) dark-zone centroblasts. To discover B cell genes regulated by IRF8, we transfected purified primary tonsillar B cells with enhanced green fluorescent protein-tagged IRF8, generated small interfering RNA knockdowns of IRF8 expression in a mouse B cell lymphoma cell line, and examined the effects of a null mutation of IRF8 on B cells. Each approach identified activation-induced cytidine deaminase (AICDA) and BCL6 as targets of transcriptional activation. Chromatin immunoprecipitation studies demonstrated in vivo occupancy of 5' sequences of both genes by IRF8 protein. These results suggest previously unappreciated roles for IRF8 in the transcriptional regulation of B cell GC reactions that include direct regulation of AICDA and BCL6.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 23, 2006

Volume

203

Issue

1

Start / End Page

63 / 72

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins c-bcl-6
  • Palatine Tonsil
  • Oligonucleotide Array Sequence Analysis
  • Mice, Knockout
  • Mice
  • Interferon Regulatory Factors
  • Immunology
  • Humans
  • Germinal Center
  • Gene Expression Regulation
 

Citation

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Lee, C. H., Melchers, M., Wang, H., Torrey, T. A., Slota, R., Qi, C.-F., … Morse, H. C. (2006). Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein. J Exp Med, 203(1), 63–72. https://doi.org/10.1084/jem.20051450
Lee, Chang Hoon, Mark Melchers, Hongsheng Wang, Ted A. Torrey, Rebecca Slota, Chen-Feng Qi, Ji Young Kim, et al. “Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein.J Exp Med 203, no. 1 (January 23, 2006): 63–72. https://doi.org/10.1084/jem.20051450.
Lee CH, Melchers M, Wang H, Torrey TA, Slota R, Qi C-F, et al. Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein. J Exp Med. 2006 Jan 23;203(1):63–72.
Lee, Chang Hoon, et al. “Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein.J Exp Med, vol. 203, no. 1, Jan. 2006, pp. 63–72. Pubmed, doi:10.1084/jem.20051450.
Lee CH, Melchers M, Wang H, Torrey TA, Slota R, Qi C-F, Kim JY, Lugar P, Kong HJ, Farrington L, van der Zouwen B, Zhou JX, Lougaris V, Lipsky PE, Grammer AC, Morse HC. Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein. J Exp Med. 2006 Jan 23;203(1):63–72.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 23, 2006

Volume

203

Issue

1

Start / End Page

63 / 72

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins c-bcl-6
  • Palatine Tonsil
  • Oligonucleotide Array Sequence Analysis
  • Mice, Knockout
  • Mice
  • Interferon Regulatory Factors
  • Immunology
  • Humans
  • Germinal Center
  • Gene Expression Regulation