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Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor κB2 in Regulating Circulating B Cell Numbers

The number of circulating follicular B lymphocytes is normally kept within a precise range despite their dispersion through the body and daily overproduction of precursors in the bone marrow. By establishing a genome wide recessive mutation screen in C57BL/6 mice to identify critical components of i...

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Autores principales: Miosge, Lisa A., Blasioli, Julie, Blery, Mathieu, Goodnow, Christopher C.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194042/
https://www.ncbi.nlm.nih.gov/pubmed/12391023
http://dx.doi.org/10.1084/jem.20020959
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author Miosge, Lisa A.
Blasioli, Julie
Blery, Mathieu
Goodnow, Christopher C.
author_facet Miosge, Lisa A.
Blasioli, Julie
Blery, Mathieu
Goodnow, Christopher C.
author_sort Miosge, Lisa A.
collection PubMed
description The number of circulating follicular B lymphocytes is normally kept within a precise range despite their dispersion through the body and daily overproduction of precursors in the bone marrow. By establishing a genome wide recessive mutation screen in C57BL/6 mice to identify critical components of immune system regulation, we identified a mutant strain with selective deficiency in recirculating B cells but not immature or peritoneal B1 cells. Analysis of mixed bone marrow chimeras established that the mutation affects a cell autonomous process within B cells that is required for their accumulation after emigrating to peripheral lymphoid organs. The defect is caused by a point mutation in the gene encoding transcription factor nuclear factor (NF)-κB2, terminating the encoded protein within the DNA-binding domain. These findings establish the feasibility of analyzing immune regulation by genome wide mutant screens and demonstrates an intrinsic requirement for NF-κB2 in regulating circulating follicular B cell numbers.
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spelling pubmed-21940422008-04-11 Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor κB2 in Regulating Circulating B Cell Numbers Miosge, Lisa A. Blasioli, Julie Blery, Mathieu Goodnow, Christopher C. J Exp Med Brief Definitive Report The number of circulating follicular B lymphocytes is normally kept within a precise range despite their dispersion through the body and daily overproduction of precursors in the bone marrow. By establishing a genome wide recessive mutation screen in C57BL/6 mice to identify critical components of immune system regulation, we identified a mutant strain with selective deficiency in recirculating B cells but not immature or peritoneal B1 cells. Analysis of mixed bone marrow chimeras established that the mutation affects a cell autonomous process within B cells that is required for their accumulation after emigrating to peripheral lymphoid organs. The defect is caused by a point mutation in the gene encoding transcription factor nuclear factor (NF)-κB2, terminating the encoded protein within the DNA-binding domain. These findings establish the feasibility of analyzing immune regulation by genome wide mutant screens and demonstrates an intrinsic requirement for NF-κB2 in regulating circulating follicular B cell numbers. The Rockefeller University Press 2002-10-21 /pmc/articles/PMC2194042/ /pubmed/12391023 http://dx.doi.org/10.1084/jem.20020959 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 Brief Definitive Report
Miosge, Lisa A.
Blasioli, Julie
Blery, Mathieu
Goodnow, Christopher C.
Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor κB2 in Regulating Circulating B Cell Numbers
title Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor κB2 in Regulating Circulating B Cell Numbers
title_full Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor κB2 in Regulating Circulating B Cell Numbers
title_fullStr Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor κB2 in Regulating Circulating B Cell Numbers
title_full_unstemmed Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor κB2 in Regulating Circulating B Cell Numbers
title_short Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor κB2 in Regulating Circulating B Cell Numbers
title_sort analysis of an ethylnitrosourea-generated mouse mutation defines a cell intrinsic role of nuclear factor κb2 in regulating circulating b cell numbers
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194042/
https://www.ncbi.nlm.nih.gov/pubmed/12391023
http://dx.doi.org/10.1084/jem.20020959
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