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BCL6 Controls the Expression of the B7-1/CD80 Costimulatory Receptor in Germinal Center B Cells
The BCL6 proto-oncogene encodes a transcriptional repressor required for the development of germinal centers (GCs) and implicated in the pathogenesis of GC-derived B cell lymphoma. Understanding the precise role of BCL6 in normal GC formation and in lymphomagenesis depends on the identification of g...
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194068/ https://www.ncbi.nlm.nih.gov/pubmed/12860928 http://dx.doi.org/10.1084/jem.20021395 |
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author | Niu, Huifeng Cattoretti, Giorgio Dalla-Favera, Riccardo |
author_facet | Niu, Huifeng Cattoretti, Giorgio Dalla-Favera, Riccardo |
author_sort | Niu, Huifeng |
collection | PubMed |
description | The BCL6 proto-oncogene encodes a transcriptional repressor required for the development of germinal centers (GCs) and implicated in the pathogenesis of GC-derived B cell lymphoma. Understanding the precise role of BCL6 in normal GC formation and in lymphomagenesis depends on the identification of genes that are direct targets of its transcriptional repression. Here we report that BCL6 directly controls the expression of B7–1/CD80, a costimulatory receptor involved in B–T cell interactions critical for the development of T cell–mediated antibody responses. Upon CD40 signaling, transcription of the CD80 gene is induced by the nuclear factor (NF)-κB transcription factor. Our results show that BCL6 prevents CD40-induced expression of CD80 by binding its promoter region in vivo and suppressing its transcriptional activation by NF-κB. Consistent with a physiologic role for BCL6 in suppressing CD80, the expression of these two genes is mutually exclusive in B cells, and BCL6-defective mice show increased expression of CD80 in B cells. The results suggest that BCL6 may directly control the ability of B cell to interact with T cells during normal GC development. In addition, these findings imply that T–B cell interactions may be disrupted in B cell lymphoma expressing deregulated BCL6 genes. |
format | Text |
id | pubmed-2194068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21940682008-04-11 BCL6 Controls the Expression of the B7-1/CD80 Costimulatory Receptor in Germinal Center B Cells Niu, Huifeng Cattoretti, Giorgio Dalla-Favera, Riccardo J Exp Med Article The BCL6 proto-oncogene encodes a transcriptional repressor required for the development of germinal centers (GCs) and implicated in the pathogenesis of GC-derived B cell lymphoma. Understanding the precise role of BCL6 in normal GC formation and in lymphomagenesis depends on the identification of genes that are direct targets of its transcriptional repression. Here we report that BCL6 directly controls the expression of B7–1/CD80, a costimulatory receptor involved in B–T cell interactions critical for the development of T cell–mediated antibody responses. Upon CD40 signaling, transcription of the CD80 gene is induced by the nuclear factor (NF)-κB transcription factor. Our results show that BCL6 prevents CD40-induced expression of CD80 by binding its promoter region in vivo and suppressing its transcriptional activation by NF-κB. Consistent with a physiologic role for BCL6 in suppressing CD80, the expression of these two genes is mutually exclusive in B cells, and BCL6-defective mice show increased expression of CD80 in B cells. The results suggest that BCL6 may directly control the ability of B cell to interact with T cells during normal GC development. In addition, these findings imply that T–B cell interactions may be disrupted in B cell lymphoma expressing deregulated BCL6 genes. The Rockefeller University Press 2003-07-21 /pmc/articles/PMC2194068/ /pubmed/12860928 http://dx.doi.org/10.1084/jem.20021395 Text en Copyright © 2003, 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 | Article Niu, Huifeng Cattoretti, Giorgio Dalla-Favera, Riccardo BCL6 Controls the Expression of the B7-1/CD80 Costimulatory Receptor in Germinal Center B Cells |
title | BCL6 Controls the Expression of the B7-1/CD80 Costimulatory Receptor in Germinal Center B Cells |
title_full | BCL6 Controls the Expression of the B7-1/CD80 Costimulatory Receptor in Germinal Center B Cells |
title_fullStr | BCL6 Controls the Expression of the B7-1/CD80 Costimulatory Receptor in Germinal Center B Cells |
title_full_unstemmed | BCL6 Controls the Expression of the B7-1/CD80 Costimulatory Receptor in Germinal Center B Cells |
title_short | BCL6 Controls the Expression of the B7-1/CD80 Costimulatory Receptor in Germinal Center B Cells |
title_sort | bcl6 controls the expression of the b7-1/cd80 costimulatory receptor in germinal center b cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194068/ https://www.ncbi.nlm.nih.gov/pubmed/12860928 http://dx.doi.org/10.1084/jem.20021395 |
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