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Article: Regulation of B-lymphocyte negative and positive selection by tyrosine phosphatase CD45

TitleRegulation of B-lymphocyte negative and positive selection by tyrosine phosphatase CD45
Authors
Issue Date1996
Citation
Nature, 1996, v. 381, n. 6580, p. 325-328 How to Cite?
AbstractElimination of self-reactive B cells must be balanced against the need for B-cell diversity for antibody responses to pathogens. To analyse factors that determine the extent of B-cell negative selection, we crossed CD45-deficient mice with mice carrying immunoglobulin transgenes specific for hen egg lysozyme (HEL). CD45 positively regulates antigen-receptor signalling and CD45-deficient HEL-specific B cells gave diminished signalling in response to HEL. Significantly, few mature CD45(-/-) B cells accumulated, despite normal immature B-cell production. Circulating HEL autoantigen mediates negative selection of mature CD45(+/+) HEL binding B cells but, in striking contrast, the autoantigen positively selected CD45(-/-) HEL-binding B cells, promoting their accumulation as long-lived IgD(hi) cells. These findings are consistent with a signal-threshold model for B-cell selection and demonstrate that changes in antigen receptor signalling can cause high-affinity self-reactive B cells to be actively retained instead of eliminated, thus revealing a potential mechanism for inherited susceptibility to autoimmune disease.
Persistent Identifierhttp://hdl.handle.net/10722/292504
ISSN
2023 Impact Factor: 50.5
2023 SCImago Journal Rankings: 18.509
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCyster, Jason G.-
dc.contributor.authorHealy, James I.-
dc.contributor.authorKishihara, Kenji-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorThomas, Matthew L.-
dc.contributor.authorGoodnow, Christopher C.-
dc.date.accessioned2020-11-17T14:56:37Z-
dc.date.available2020-11-17T14:56:37Z-
dc.date.issued1996-
dc.identifier.citationNature, 1996, v. 381, n. 6580, p. 325-328-
dc.identifier.issn0028-0836-
dc.identifier.urihttp://hdl.handle.net/10722/292504-
dc.description.abstractElimination of self-reactive B cells must be balanced against the need for B-cell diversity for antibody responses to pathogens. To analyse factors that determine the extent of B-cell negative selection, we crossed CD45-deficient mice with mice carrying immunoglobulin transgenes specific for hen egg lysozyme (HEL). CD45 positively regulates antigen-receptor signalling and CD45-deficient HEL-specific B cells gave diminished signalling in response to HEL. Significantly, few mature CD45(-/-) B cells accumulated, despite normal immature B-cell production. Circulating HEL autoantigen mediates negative selection of mature CD45(+/+) HEL binding B cells but, in striking contrast, the autoantigen positively selected CD45(-/-) HEL-binding B cells, promoting their accumulation as long-lived IgD(hi) cells. These findings are consistent with a signal-threshold model for B-cell selection and demonstrate that changes in antigen receptor signalling can cause high-affinity self-reactive B cells to be actively retained instead of eliminated, thus revealing a potential mechanism for inherited susceptibility to autoimmune disease.-
dc.languageeng-
dc.relation.ispartofNature-
dc.titleRegulation of B-lymphocyte negative and positive selection by tyrosine phosphatase CD45-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/381325a0-
dc.identifier.pmid8692271-
dc.identifier.scopuseid_2-s2.0-0030023652-
dc.identifier.volume381-
dc.identifier.issue6580-
dc.identifier.spage325-
dc.identifier.epage328-
dc.identifier.isiWOS:A1996UM40300057-
dc.identifier.issnl0028-0836-

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