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Article: Cells that produce deleterious autoreactive antibodies are vulnerable to suicide

TitleCells that produce deleterious autoreactive antibodies are vulnerable to suicide
Authors
Issue Date2008
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
Citation
Journal Of Immunology, 2008, v. 181 n. 3, p. 2246-2257 How to Cite?
AbstractIt is puzzling how autoreactive B cells that escape self-tolerance mechanisms manage to produce Abs that target vital cellular processes without succumbing themselves to the potentially deleterious effects of these proteins. We report that censorship indeed exists at this level: when the Ab synthesis in the cell is up-regulated in IL-6-enriched environments (e.g., adjuvant-primed mouse peritoneum), the cell dies of the increased intracellular binding between the Ab and the cellular autoantigen. In the case in which telomerase is the autoantigen, mouse hybridoma cells synthesizing such an autoantibody, which appeared to grow well in culture, could not grow in syngeneic BALB/c mice to form ascites, but grew nevertheless in athymic siblings. Culture experiments demonstrated that peritoneal cell-derived IL-6 (and accessory factors) affected the growth and functions of the hybridoma cells, including the induction of mitochondria-based apoptosis. Electron microscopy revealed an abundance of Abs in the nuclear chromatin of IL-6-stimulated cells, presumably piggy-backed there by telomerase from the cytosol. This nuclear presence was confirmed by light microscopy analysis of isolated nuclei. In two other cases, hybridoma cells synthesizing an autoantibody to GTP or osteopontin also showed similar growth inhibition in vivo. In all cases, Ab function was crucial to the demise of the cells. Thus, autoreactive cells, which synthesize autoantibodies to certain intracellular Ags, live delicately between life and death depending on the cytokine microenvironment. Paradoxically, IL-6, which is normally growth-potentiating for B cells, is proapoptotic for these cells. The findings reveal potential strategies and targets for immunotherapy. Copyright © 2008 by The American Association of Immunologists, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/148575
ISSN
2015 Impact Factor: 4.985
2015 SCImago Journal Rankings: 3.549
References

 

DC FieldValueLanguage
dc.contributor.authorNiu, Hen_US
dc.contributor.authorLeung, DTMen_US
dc.contributor.authorChun, HMen_US
dc.contributor.authorLaw, ECYen_US
dc.contributor.authorTam, FCHen_US
dc.contributor.authorLim, PLen_US
dc.date.accessioned2012-05-29T06:13:49Z-
dc.date.available2012-05-29T06:13:49Z-
dc.date.issued2008en_US
dc.identifier.citationJournal Of Immunology, 2008, v. 181 n. 3, p. 2246-2257en_US
dc.identifier.issn0022-1767en_US
dc.identifier.urihttp://hdl.handle.net/10722/148575-
dc.description.abstractIt is puzzling how autoreactive B cells that escape self-tolerance mechanisms manage to produce Abs that target vital cellular processes without succumbing themselves to the potentially deleterious effects of these proteins. We report that censorship indeed exists at this level: when the Ab synthesis in the cell is up-regulated in IL-6-enriched environments (e.g., adjuvant-primed mouse peritoneum), the cell dies of the increased intracellular binding between the Ab and the cellular autoantigen. In the case in which telomerase is the autoantigen, mouse hybridoma cells synthesizing such an autoantibody, which appeared to grow well in culture, could not grow in syngeneic BALB/c mice to form ascites, but grew nevertheless in athymic siblings. Culture experiments demonstrated that peritoneal cell-derived IL-6 (and accessory factors) affected the growth and functions of the hybridoma cells, including the induction of mitochondria-based apoptosis. Electron microscopy revealed an abundance of Abs in the nuclear chromatin of IL-6-stimulated cells, presumably piggy-backed there by telomerase from the cytosol. This nuclear presence was confirmed by light microscopy analysis of isolated nuclei. In two other cases, hybridoma cells synthesizing an autoantibody to GTP or osteopontin also showed similar growth inhibition in vivo. In all cases, Ab function was crucial to the demise of the cells. Thus, autoreactive cells, which synthesize autoantibodies to certain intracellular Ags, live delicately between life and death depending on the cytokine microenvironment. Paradoxically, IL-6, which is normally growth-potentiating for B cells, is proapoptotic for these cells. The findings reveal potential strategies and targets for immunotherapy. Copyright © 2008 by The American Association of Immunologists, Inc.en_US
dc.languageengen_US
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.orgen_US
dc.relation.ispartofJournal of Immunologyen_US
dc.titleCells that produce deleterious autoreactive antibodies are vulnerable to suicideen_US
dc.typeArticleen_US
dc.identifier.emailLaw, ECY:ericlaw@pathology.hku.hken_US
dc.identifier.authorityLaw, ECY=rp01586en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.scopuseid_2-s2.0-49649110968en_US
dc.identifier.hkuros221015-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-49649110968&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume181en_US
dc.identifier.issue3en_US
dc.identifier.spage2246en_US
dc.identifier.epage2257en_US
dc.publisher.placeUnited Statesen_US

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