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Resistance to CpG DNA-induced autoimmunity through tolerogenic B cell antigen receptor ERK signaling

Rui, Lixin; Garcia De Vinuesa, Maria Carola; Blasioli, Julie; Goodnow, Christopher

Description

CpG sequences in self-DNA are an important potential trigger for autoantibody secretion in systemic lupus and other systemic autoimmune disorders. It is not known how this ubiquitous threat may be controlled by active mechanisms for maintaining self tolerance. Here we show that two distinct mechanisms oppose autoantibody secretion induced by CpG DNA in anergic B cells that are constantly binding self-antigen. Uncoupling of the antigen receptor (BCR) from a calcineurin-dependent pathway prevents...[Show more]

dc.contributor.authorRui, Lixin
dc.contributor.authorGarcia De Vinuesa, Maria Carola
dc.contributor.authorBlasioli, Julie
dc.contributor.authorGoodnow, Christopher
dc.date.accessioned2015-12-13T23:13:53Z
dc.date.available2015-12-13T23:13:53Z
dc.identifier.issn1529-2908
dc.identifier.urihttp://hdl.handle.net/1885/88341
dc.description.abstractCpG sequences in self-DNA are an important potential trigger for autoantibody secretion in systemic lupus and other systemic autoimmune disorders. It is not known how this ubiquitous threat may be controlled by active mechanisms for maintaining self tolerance. Here we show that two distinct mechanisms oppose autoantibody secretion induced by CpG DNA in anergic B cells that are constantly binding self-antigen. Uncoupling of the antigen receptor (BCR) from a calcineurin-dependent pathway prevents signals that synergize with CpG DNA for proliferation. The BCR does not become desensitized by activating the extracellular response kinase (ERK) MAP kinase pathway, however, and continuous self-antigen signaling to ERK inhibits CpG DNA-induced plasma cell differentiation. These two mechanisms seem to act as a general control against autoantibody production elicited by Toll-like receptors, and their regulation of T cell-independent responses to Toll-like receptor 9 (TLR9) is probably crucial for resistance to systemic autoimmunity.
dc.publisherNature Publishing Group
dc.sourceNature Immunology
dc.subjectKeywords: autoantibody; B lymphocyte antigen; calcineurin; DNA; lymphocyte antigen receptor; mitogen activated protein kinase; toll like receptor; toll like receptor 9; antibody production; antibody response; antigen binding; article; autoimmune disease; autoimmuni
dc.titleResistance to CpG DNA-induced autoimmunity through tolerogenic B cell antigen receptor ERK signaling
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume4
dc.date.issued2003
local.identifier.absfor110703 - Autoimmunity
local.identifier.ariespublicationMigratedxPub18005
local.type.statusPublished Version
local.contributor.affiliationRui, Lixin, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationGarcia De Vinuesa, Maria Carola, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationBlasioli, Julie, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationGoodnow, Christopher, College of Medicine, Biology and Environment, ANU
local.bibliographicCitation.issue6
local.bibliographicCitation.startpage594
local.bibliographicCitation.lastpage600
local.identifier.doi10.1038/ni924
dc.date.updated2015-12-12T08:36:10Z
local.identifier.scopusID2-s2.0-0037501347
CollectionsANU Research Publications

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