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

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 lymphocy...

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Autores principales: Lee, Chang Hoon, Melchers, Mark, Wang, Hongsheng, Torrey, Ted A., Slota, Rebecca, Qi, Chen-Feng, Kim, Ji Young, Lugar, Patricia, Kong, Hee Jeong, Farrington, Lila, van der Zouwen, Boris, Zhou, Jeff X., Lougaris, Vassilios, Lipsky, Peter E., Grammer, Amrie C., Morse, Herbert C.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118063/
https://www.ncbi.nlm.nih.gov/pubmed/16380510
http://dx.doi.org/10.1084/jem.20051450
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author Lee, Chang Hoon
Melchers, Mark
Wang, Hongsheng
Torrey, Ted A.
Slota, Rebecca
Qi, Chen-Feng
Kim, Ji Young
Lugar, Patricia
Kong, Hee Jeong
Farrington, Lila
van der Zouwen, Boris
Zhou, Jeff X.
Lougaris, Vassilios
Lipsky, Peter E.
Grammer, Amrie C.
Morse, Herbert C.
author_facet Lee, Chang Hoon
Melchers, Mark
Wang, Hongsheng
Torrey, Ted A.
Slota, Rebecca
Qi, Chen-Feng
Kim, Ji Young
Lugar, Patricia
Kong, Hee Jeong
Farrington, Lila
van der Zouwen, Boris
Zhou, Jeff X.
Lougaris, Vassilios
Lipsky, Peter E.
Grammer, Amrie C.
Morse, Herbert C.
author_sort Lee, Chang Hoon
collection PubMed
description 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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spelling pubmed-21180632007-12-13 Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein Lee, Chang Hoon Melchers, Mark Wang, Hongsheng Torrey, Ted A. Slota, Rebecca Qi, Chen-Feng Kim, Ji Young Lugar, Patricia Kong, Hee Jeong Farrington, Lila van der Zouwen, Boris Zhou, Jeff X. Lougaris, Vassilios Lipsky, Peter E. Grammer, Amrie C. Morse, Herbert C. J Exp Med Articles 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. The Rockefeller University Press 2006-01-23 /pmc/articles/PMC2118063/ /pubmed/16380510 http://dx.doi.org/10.1084/jem.20051450 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Lee, Chang Hoon
Melchers, Mark
Wang, Hongsheng
Torrey, Ted A.
Slota, Rebecca
Qi, Chen-Feng
Kim, Ji Young
Lugar, Patricia
Kong, Hee Jeong
Farrington, Lila
van der Zouwen, Boris
Zhou, Jeff X.
Lougaris, Vassilios
Lipsky, Peter E.
Grammer, Amrie C.
Morse, Herbert C.
Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein
title Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein
title_full Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein
title_fullStr Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein
title_full_unstemmed Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein
title_short Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein
title_sort regulation of the germinal center gene program by interferon (ifn) regulatory factor 8/ifn consensus sequence-binding protein
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118063/
https://www.ncbi.nlm.nih.gov/pubmed/16380510
http://dx.doi.org/10.1084/jem.20051450
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