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Gene dose-dependent maturation and receptor editing of B cells expressing immunoglobulin (Ig)G1 or IgM/IgG1 tail antigen receptors

Pogue, Sarah; Goodnow, Christopher

Description

Conserved differences between the transmembrane and cytoplasmic domains of membrane immunoglobulin (Ig)M and IgG may alter the function of antigen receptors on naive versus memory B cells. Here, we compare the ability of these domains to signal B cell allelic exclusion and maturation in transgenic mice. A lysozyme-binding antibody was expressed in parallel sets of mice as IgM, IgG1, or a chimeric receptor with IgM extracellular domains and transmembrane/cytoplasmic domains of IgG1. Like IgM,...[Show more]

dc.contributor.authorPogue, Sarah
dc.contributor.authorGoodnow, Christopher
dc.date.accessioned2015-12-13T23:16:51Z
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/1885/89613
dc.description.abstractConserved differences between the transmembrane and cytoplasmic domains of membrane immunoglobulin (Ig)M and IgG may alter the function of antigen receptors on naive versus memory B cells. Here, we compare the ability of these domains to signal B cell allelic exclusion and maturation in transgenic mice. A lysozyme-binding antibody was expressed in parallel sets of mice as IgM, IgG1, or a chimeric receptor with IgM extracellular domains and transmembrane/cytoplasmic domains of IgG1. Like IgM, the IgG1 or chimeric IgM/G receptors triggered heavy chain allelic exclusion and supported development of mature CD21+ B cells. Many of the IgG or IgM/G B cells became CD21(high) and downregulated their IgG and IgM/G receptors spontaneously, resembling memory B cells and B cells with mutations that exaggerate B cell antigen receptor signaling. Unlike IgM-transgenic mice, 'edited' B cells that carry non-hen egg lysozyme binding receptors preferentially accumulated in IgG and IgM/G mice. This was most extreme in lines with the highest transgene copy number and diminished in variant offspring with fewer copies. The sensitivity of B cell maturation to transgene copy number conferred by the IgG transmembrane and cytoplasmic domains may explain the diverse phenotypes found in other IgG-transgenic mouse strains and may reflect exaggerated signaling.
dc.publisherRockefeller University Press
dc.sourceJournal of Experimental Medicine
dc.subjectKeywords: immunoglobulin G1; immunoglobulin M; lymphocyte antigen receptor; animal cell; article; B lymphocyte; cell maturation; controlled study; gene dosage; gene number; mouse; nonhuman; priority journal; protein domain; transgene; transgenic mouse; Animals; B-L Allelic exclusion; B lymphocyte; Development; Isotype switch; Transgene
dc.titleGene dose-dependent maturation and receptor editing of B cells expressing immunoglobulin (Ig)G1 or IgM/IgG1 tail antigen receptors
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume191
dc.date.issued2000
local.identifier.absfor110703 - Autoimmunity
local.identifier.ariespublicationMigratedxPub19682
local.type.statusPublished Version
local.contributor.affiliationPogue, Sarah, Medarex, Inc.
local.contributor.affiliationGoodnow, Christopher, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue6
local.bibliographicCitation.startpage1031
local.bibliographicCitation.lastpage44
local.identifier.doi10.1084/jem.191.6.1031
dc.date.updated2015-12-12T08:50:00Z
local.identifier.scopusID2-s2.0-0034689025
CollectionsANU Research Publications

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