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Global analysis of B cell selection using an immunoglobulin light chain–mediated model of autoreactivity

The important subtleties of B cell tolerance are best understood in a diverse immunoglobulin (Ig) repertoire context encoding a full spectrum of autoreactivity. To achieve this, we used mice expressing Igκ transgenes that confer varying degrees of autoreactivity within a diverse heavy chain (HC) rep...

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Autores principales: Andrews, Sarah F., Zhang, Qingzhao, Lim, Samuel, Li, Lie, Lee, Jane-Hwei, Zheng, Nai-Ying, Huang, Min, Taylor, William M., Farris, A. Darise, Ni, Dongyao, Meng, Wenzhao, Luning Prak, Eline T., Wilson, Patrick C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549719/
https://www.ncbi.nlm.nih.gov/pubmed/23267014
http://dx.doi.org/10.1084/jem.20120525
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author Andrews, Sarah F.
Zhang, Qingzhao
Lim, Samuel
Li, Lie
Lee, Jane-Hwei
Zheng, Nai-Ying
Huang, Min
Taylor, William M.
Farris, A. Darise
Ni, Dongyao
Meng, Wenzhao
Luning Prak, Eline T.
Wilson, Patrick C.
author_facet Andrews, Sarah F.
Zhang, Qingzhao
Lim, Samuel
Li, Lie
Lee, Jane-Hwei
Zheng, Nai-Ying
Huang, Min
Taylor, William M.
Farris, A. Darise
Ni, Dongyao
Meng, Wenzhao
Luning Prak, Eline T.
Wilson, Patrick C.
author_sort Andrews, Sarah F.
collection PubMed
description The important subtleties of B cell tolerance are best understood in a diverse immunoglobulin (Ig) repertoire context encoding a full spectrum of autoreactivity. To achieve this, we used mice expressing Igκ transgenes that confer varying degrees of autoreactivity within a diverse heavy chain (HC) repertoire. These transgenes, coupled with a biomarker to identify receptor-edited cells and combined with expression cloning of B cell receptors, allowed us to analyze tolerance throughout B cell development. We found that both the nature of the autoantigen and the Ig HC versus light chain (LC) contribution to autoreactivity dictate the developmental stage and mechanism of tolerance. Furthermore, although selection begins in the bone marrow, over one third of primary tolerance occurs in the periphery at the late transitional developmental stage. Notably, we demonstrate that the LC has profound effects on tolerance and can lead to exacerbated autoantibody production.
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spelling pubmed-35497192013-07-14 Global analysis of B cell selection using an immunoglobulin light chain–mediated model of autoreactivity Andrews, Sarah F. Zhang, Qingzhao Lim, Samuel Li, Lie Lee, Jane-Hwei Zheng, Nai-Ying Huang, Min Taylor, William M. Farris, A. Darise Ni, Dongyao Meng, Wenzhao Luning Prak, Eline T. Wilson, Patrick C. J Exp Med Article The important subtleties of B cell tolerance are best understood in a diverse immunoglobulin (Ig) repertoire context encoding a full spectrum of autoreactivity. To achieve this, we used mice expressing Igκ transgenes that confer varying degrees of autoreactivity within a diverse heavy chain (HC) repertoire. These transgenes, coupled with a biomarker to identify receptor-edited cells and combined with expression cloning of B cell receptors, allowed us to analyze tolerance throughout B cell development. We found that both the nature of the autoantigen and the Ig HC versus light chain (LC) contribution to autoreactivity dictate the developmental stage and mechanism of tolerance. Furthermore, although selection begins in the bone marrow, over one third of primary tolerance occurs in the periphery at the late transitional developmental stage. Notably, we demonstrate that the LC has profound effects on tolerance and can lead to exacerbated autoantibody production. The Rockefeller University Press 2013-01-14 /pmc/articles/PMC3549719/ /pubmed/23267014 http://dx.doi.org/10.1084/jem.20120525 Text en © 2013 Andrews et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Andrews, Sarah F.
Zhang, Qingzhao
Lim, Samuel
Li, Lie
Lee, Jane-Hwei
Zheng, Nai-Ying
Huang, Min
Taylor, William M.
Farris, A. Darise
Ni, Dongyao
Meng, Wenzhao
Luning Prak, Eline T.
Wilson, Patrick C.
Global analysis of B cell selection using an immunoglobulin light chain–mediated model of autoreactivity
title Global analysis of B cell selection using an immunoglobulin light chain–mediated model of autoreactivity
title_full Global analysis of B cell selection using an immunoglobulin light chain–mediated model of autoreactivity
title_fullStr Global analysis of B cell selection using an immunoglobulin light chain–mediated model of autoreactivity
title_full_unstemmed Global analysis of B cell selection using an immunoglobulin light chain–mediated model of autoreactivity
title_short Global analysis of B cell selection using an immunoglobulin light chain–mediated model of autoreactivity
title_sort global analysis of b cell selection using an immunoglobulin light chain–mediated model of autoreactivity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549719/
https://www.ncbi.nlm.nih.gov/pubmed/23267014
http://dx.doi.org/10.1084/jem.20120525
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