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Analysis of an ethylnitrosourea-generated mouse mutation defines a cell intrinsic role of nuclear factor kB2 in regulating circulating B cell numbers

Miosge, Lisa; Blasioli, Julie; Blery, Mathieu; Goodnow, Christopher

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...[Show more]

dc.contributor.authorMiosge, Lisa
dc.contributor.authorBlasioli, Julie
dc.contributor.authorBlery, Mathieu
dc.contributor.authorGoodnow, Christopher
dc.date.accessioned2015-12-13T23:40:45Z
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/1885/94596
dc.description.abstractThe 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.
dc.publisherRockefeller University Press
dc.sourceJournal of Experimental Medicine
dc.subjectKeywords: ethylnitrosourea; immunoglobulin enhancer binding protein; animal cell; animal tissue; article; B lymphocyte; bone marrow cell; chimera; controlled study; genome; immunoregulation; lymphoid organ; male; mouse; nonhuman; point mutation; priority journal; p B lymphocytes; Ethylnitrosourea; Follicular; Mutagenesis; Rel/NF-?B
dc.titleAnalysis of an ethylnitrosourea-generated mouse mutation defines a cell intrinsic role of nuclear factor kB2 in regulating circulating B cell numbers
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume196
dc.date.issued2002
local.identifier.absfor110703 - Autoimmunity
local.identifier.ariespublicationMigratedxPub24214
local.type.statusPublished Version
local.contributor.affiliationMiosge, Lisa, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationBlasioli, Julie, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationBlery, Mathieu , College of Medicine, Biology and Environment, ANU
local.contributor.affiliationGoodnow, Christopher, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue8
local.bibliographicCitation.startpage1113
local.bibliographicCitation.lastpage1119
local.identifier.doi10.1084/jem.20020959
dc.date.updated2015-12-12T09:30:15Z
local.identifier.scopusID2-s2.0-0037152174
CollectionsANU Research Publications

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