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Regulation of AID expression in the immune response
The B cell–specific enzyme activation-induced cytidine deaminase (AID) has been shown to be essential for isotype switching and affinity maturation of antibody genes during the immune response. Conversely, AID activity has also been linked to autoimmunity and tumorigenesis. Determining how AID expre...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118564/ https://www.ncbi.nlm.nih.gov/pubmed/17452520 http://dx.doi.org/10.1084/jem.20061952 |
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author | Crouch, Elizabeth E. Li, Zhiyu Takizawa, Makiko Fichtner-Feigl, Stefan Gourzi, Polyxeni Montaño, Carolina Feigenbaum, Lionel Wilson, Patrick Janz, Siegfried Papavasiliou, F. Nina Casellas, Rafael |
author_facet | Crouch, Elizabeth E. Li, Zhiyu Takizawa, Makiko Fichtner-Feigl, Stefan Gourzi, Polyxeni Montaño, Carolina Feigenbaum, Lionel Wilson, Patrick Janz, Siegfried Papavasiliou, F. Nina Casellas, Rafael |
author_sort | Crouch, Elizabeth E. |
collection | PubMed |
description | The B cell–specific enzyme activation-induced cytidine deaminase (AID) has been shown to be essential for isotype switching and affinity maturation of antibody genes during the immune response. Conversely, AID activity has also been linked to autoimmunity and tumorigenesis. Determining how AID expression is regulated in vivo is therefore central to understanding its role in health and disease. Here we use phylogenetic footprinting and high-resolution histone acetylation mapping to accurately demarcate AID gene regulatory boundaries. Based on this strategy, we identify a novel, positive regulatory element required for AID transcription. Furthermore, we generate two AID indicator mouse strains using bacterial artificial chromosomes that faithfully recapitulate endogenous AID expression. The first strain uses a green fluorescent protein reporter to identify B cells that actively express AID during the immune response. In the second strain, AID transcription affects the permanent expression of a yellow fluorescent protein reporter in post–germinal center and terminally differentiated lymphocytes. We demonstrate the usefulness of these novel strains by resolving recent contradictory observations on AID expression during B cell ontogeny. |
format | Text |
id | pubmed-2118564 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21185642007-12-13 Regulation of AID expression in the immune response Crouch, Elizabeth E. Li, Zhiyu Takizawa, Makiko Fichtner-Feigl, Stefan Gourzi, Polyxeni Montaño, Carolina Feigenbaum, Lionel Wilson, Patrick Janz, Siegfried Papavasiliou, F. Nina Casellas, Rafael J Exp Med Articles The B cell–specific enzyme activation-induced cytidine deaminase (AID) has been shown to be essential for isotype switching and affinity maturation of antibody genes during the immune response. Conversely, AID activity has also been linked to autoimmunity and tumorigenesis. Determining how AID expression is regulated in vivo is therefore central to understanding its role in health and disease. Here we use phylogenetic footprinting and high-resolution histone acetylation mapping to accurately demarcate AID gene regulatory boundaries. Based on this strategy, we identify a novel, positive regulatory element required for AID transcription. Furthermore, we generate two AID indicator mouse strains using bacterial artificial chromosomes that faithfully recapitulate endogenous AID expression. The first strain uses a green fluorescent protein reporter to identify B cells that actively express AID during the immune response. In the second strain, AID transcription affects the permanent expression of a yellow fluorescent protein reporter in post–germinal center and terminally differentiated lymphocytes. We demonstrate the usefulness of these novel strains by resolving recent contradictory observations on AID expression during B cell ontogeny. The Rockefeller University Press 2007-05-14 /pmc/articles/PMC2118564/ /pubmed/17452520 http://dx.doi.org/10.1084/jem.20061952 Text en Copyright © 2007, 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 Crouch, Elizabeth E. Li, Zhiyu Takizawa, Makiko Fichtner-Feigl, Stefan Gourzi, Polyxeni Montaño, Carolina Feigenbaum, Lionel Wilson, Patrick Janz, Siegfried Papavasiliou, F. Nina Casellas, Rafael Regulation of AID expression in the immune response |
title | Regulation of AID expression in the immune response |
title_full | Regulation of AID expression in the immune response |
title_fullStr | Regulation of AID expression in the immune response |
title_full_unstemmed | Regulation of AID expression in the immune response |
title_short | Regulation of AID expression in the immune response |
title_sort | regulation of aid expression in the immune response |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118564/ https://www.ncbi.nlm.nih.gov/pubmed/17452520 http://dx.doi.org/10.1084/jem.20061952 |
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