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Anti–DNA B Cells in MRL/lpr Mice Show Altered Differentiation and Editing Pattern

We have studied the regulation of anti–DNA B cells in transgenic mice with a heavy chain transgene (3H9H/56R). This transgene codes for a heavy chain that forms anti–double-stranded DNA (dsDNA) antibody when paired with most members of the endogenous Vκ repertoire, but certain L chains, referred to...

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Detalles Bibliográficos
Autores principales: Li, Yijin, Li, Hui, Ni, Dongyao, Weigert, Martin
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196070/
https://www.ncbi.nlm.nih.gov/pubmed/12486097
http://dx.doi.org/10.1084/jem.20021560
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author Li, Yijin
Li, Hui
Ni, Dongyao
Weigert, Martin
author_facet Li, Yijin
Li, Hui
Ni, Dongyao
Weigert, Martin
author_sort Li, Yijin
collection PubMed
description We have studied the regulation of anti–DNA B cells in transgenic mice with a heavy chain transgene (3H9H/56R). This transgene codes for a heavy chain that forms anti–double-stranded DNA (dsDNA) antibody when paired with most members of the endogenous Vκ repertoire, but certain L chains, referred to as Vκ editors, do not sustain dsDNA binding in combination with 3H9H/56R. In the nonautoimmune 3H9H/56R BALB/c, most B cells generated do not bind DNA because the transgene itself is edited or is associated with a Vκ editor. A minor population of B cells (30%) bind dsDNA and express the λ1 light chain (known to sustain 3H9H/56R DNA binding). These 3H9/56R/λ1 B cells coexpress a κ editor, and we propose that the down-regulation of the anti-DNA BCR caused by the dual L chain expression may prevent activation of this κ/λ population. These κ/λ B cells are sequestered in the marginal zone. Here, we studied the influence of autoimmunity on expression and regulation of 3H9H/56R. In 3H9H/56R MRL/lpr mice, the expression of anti-dsDNA is vastly accelerated. Anti–dsDNA B cells use noneditor κs but, in addition, most anti–dsDNA B cells have edited the heavy chain transgene. λ1 B cells (without the coexpression of a κ editor) are found and the κ/λ1 MZ population is absent. Our results suggest that improper editing and failure to sequester autoreactive B cells may contribute to the breakdown of tolerance in MRL/lpr mice.
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spelling pubmed-21960702008-04-11 Anti–DNA B Cells in MRL/lpr Mice Show Altered Differentiation and Editing Pattern Li, Yijin Li, Hui Ni, Dongyao Weigert, Martin J Exp Med Article We have studied the regulation of anti–DNA B cells in transgenic mice with a heavy chain transgene (3H9H/56R). This transgene codes for a heavy chain that forms anti–double-stranded DNA (dsDNA) antibody when paired with most members of the endogenous Vκ repertoire, but certain L chains, referred to as Vκ editors, do not sustain dsDNA binding in combination with 3H9H/56R. In the nonautoimmune 3H9H/56R BALB/c, most B cells generated do not bind DNA because the transgene itself is edited or is associated with a Vκ editor. A minor population of B cells (30%) bind dsDNA and express the λ1 light chain (known to sustain 3H9H/56R DNA binding). These 3H9/56R/λ1 B cells coexpress a κ editor, and we propose that the down-regulation of the anti-DNA BCR caused by the dual L chain expression may prevent activation of this κ/λ population. These κ/λ B cells are sequestered in the marginal zone. Here, we studied the influence of autoimmunity on expression and regulation of 3H9H/56R. In 3H9H/56R MRL/lpr mice, the expression of anti-dsDNA is vastly accelerated. Anti–dsDNA B cells use noneditor κs but, in addition, most anti–dsDNA B cells have edited the heavy chain transgene. λ1 B cells (without the coexpression of a κ editor) are found and the κ/λ1 MZ population is absent. Our results suggest that improper editing and failure to sequester autoreactive B cells may contribute to the breakdown of tolerance in MRL/lpr mice. The Rockefeller University Press 2002-12-16 /pmc/articles/PMC2196070/ /pubmed/12486097 http://dx.doi.org/10.1084/jem.20021560 Text en Copyright © 2002, 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
Li, Yijin
Li, Hui
Ni, Dongyao
Weigert, Martin
Anti–DNA B Cells in MRL/lpr Mice Show Altered Differentiation and Editing Pattern
title Anti–DNA B Cells in MRL/lpr Mice Show Altered Differentiation and Editing Pattern
title_full Anti–DNA B Cells in MRL/lpr Mice Show Altered Differentiation and Editing Pattern
title_fullStr Anti–DNA B Cells in MRL/lpr Mice Show Altered Differentiation and Editing Pattern
title_full_unstemmed Anti–DNA B Cells in MRL/lpr Mice Show Altered Differentiation and Editing Pattern
title_short Anti–DNA B Cells in MRL/lpr Mice Show Altered Differentiation and Editing Pattern
title_sort anti–dna b cells in mrl/lpr mice show altered differentiation and editing pattern
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196070/
https://www.ncbi.nlm.nih.gov/pubmed/12486097
http://dx.doi.org/10.1084/jem.20021560
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