Analysis of Lyn/CD22 double-deficient B cells in vivo demonstrates Lyn- and CD22-independent pathways affecting BCR regulation and B cell survival

dc.contributor.authorFerry, Helen
dc.contributor.authorCockford, Tanya L
dc.contributor.authorSilver, Karlee
dc.contributor.authorRust, Nigel
dc.contributor.authorGoodnow, Christopher
dc.contributor.authorCornall, Richard J
dc.date.accessioned2015-12-13T22:55:07Z
dc.date.issued2005
dc.date.updated2015-12-11T11:08:18Z
dc.description.abstractB cell fate is determined by the strength of signals from the antigen receptor and from co-receptors that adjust the activation threshold and tune the B cell to its environment. These co-receptors have been broadly classified into inhibitory and enhancing groups, yet some, such as CD22, may have dual effects. CD22 recruits a variety of signal enhancers at the same time as Lyn-dependent phosphorylation leads to the binding of the inhibitory phosphatase SHP-1. To assess the relative importance of Lyn- and CD22-dependent and -independent pathways, we generated Lyn and CD22 single-deficient mice and Lyn/CD22 double-deficient mice expressing the MD4 immunoglobulin transgene against hen egg lysozyme (IgHEL). This genetic approach has enabled us to compare the contributions of Lyn and CD22 to B cell development in vivo, independent of BCR specificity and in the presence and absence of self-antigen. Our results show that although the effects of Lyn are dominant in negative regulation of B cell hyperactivity, Lyn and CD22 have independent and additive effects on B cell survival. These findings emphasize the subtle nature of regulation at the BCR and the usefulness of genetic complementation to dissect common and parallel pathways.
dc.identifier.issn0014-2980
dc.identifier.urihttp://hdl.handle.net/1885/82397
dc.publisherWiley-VCH Verlag GMBH
dc.sourceEuropean Journal of Immunology
dc.subjectKeywords: B lymphocyte receptor; CD22 antigen; egg protein; immunoglobulin; lysozyme; protein kinase Lyn; animal cell; animal experiment; article; autoimmunity; B lymphocyte; B lymphocyte differentiation; cell survival; controlled study; enzyme phosphorylation; fem B lymphocytes; CD22; Lyn; Lysozyme; Transgene
dc.titleAnalysis of Lyn/CD22 double-deficient B cells in vivo demonstrates Lyn- and CD22-independent pathways affecting BCR regulation and B cell survival
dc.typeJournal article
local.bibliographicCitation.issue12
local.bibliographicCitation.lastpage3663
local.bibliographicCitation.startpage3655
local.contributor.affiliationFerry, Helen, Oxford University
local.contributor.affiliationCockford, Tanya L, University of Oxford
local.contributor.affiliationSilver, Karlee, University of Oxford
local.contributor.affiliationRust, Nigel, University of Oxford
local.contributor.affiliationGoodnow, Christopher, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationCornall, Richard J, Oxford University
local.contributor.authoremailu9710462@anu.edu.au
local.contributor.authoruidGoodnow, Christopher, u9710462
local.description.embargo2037-12-31
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.absfor110703 - Autoimmunity
local.identifier.ariespublicationMigratedxPub10653
local.identifier.citationvolume35
local.identifier.doi10.1002/eji.200535247
local.identifier.scopusID2-s2.0-29744458161
local.identifier.uidSubmittedByMigrated
local.type.statusPublished Version

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