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.author | Ferry, Helen | |
dc.contributor.author | Cockford, Tanya L | |
dc.contributor.author | Silver, Karlee | |
dc.contributor.author | Rust, Nigel | |
dc.contributor.author | Goodnow, Christopher | |
dc.contributor.author | Cornall, Richard J | |
dc.date.accessioned | 2015-12-13T22:55:07Z | |
dc.date.issued | 2005 | |
dc.date.updated | 2015-12-11T11:08:18Z | |
dc.description.abstract | B 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.issn | 0014-2980 | |
dc.identifier.uri | http://hdl.handle.net/1885/82397 | |
dc.publisher | Wiley-VCH Verlag GMBH | |
dc.source | European Journal of Immunology | |
dc.subject | Keywords: 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.title | Analysis of Lyn/CD22 double-deficient B cells in vivo demonstrates Lyn- and CD22-independent pathways affecting BCR regulation and B cell survival | |
dc.type | Journal article | |
local.bibliographicCitation.issue | 12 | |
local.bibliographicCitation.lastpage | 3663 | |
local.bibliographicCitation.startpage | 3655 | |
local.contributor.affiliation | Ferry, Helen, Oxford University | |
local.contributor.affiliation | Cockford, Tanya L, University of Oxford | |
local.contributor.affiliation | Silver, Karlee, University of Oxford | |
local.contributor.affiliation | Rust, Nigel, University of Oxford | |
local.contributor.affiliation | Goodnow, Christopher, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Cornall, Richard J, Oxford University | |
local.contributor.authoremail | u9710462@anu.edu.au | |
local.contributor.authoruid | Goodnow, Christopher, u9710462 | |
local.description.embargo | 2037-12-31 | |
local.description.notes | Imported from ARIES | |
local.description.refereed | Yes | |
local.identifier.absfor | 110703 - Autoimmunity | |
local.identifier.ariespublication | MigratedxPub10653 | |
local.identifier.citationvolume | 35 | |
local.identifier.doi | 10.1002/eji.200535247 | |
local.identifier.scopusID | 2-s2.0-29744458161 | |
local.identifier.uidSubmittedBy | Migrated | |
local.type.status | Published Version |
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