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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...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
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.
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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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