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Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells

Enders, Anselm; Bouillet, Philippe; Puthalakath, Hamsa; Xu, Yeukang; Tarlinton, David M.; Strasser, Andreas

Description

During development, the stochastic process assembling the genes encoding antigen receptors invariably generates B and T lymphocytes that can recognize self-antigens. Several mechanisms have evolved to prevent the activation of these cells and the concomitant development of autoimmune disease. One such mechanism is the induction of apoptosis in developing or mature B cells by engagement of the B cell antigen receptor (BCR) in the absence of T cell help. Here we report that B lymphocytes lacking...[Show more]

dc.contributor.authorEnders, Anselm
dc.contributor.authorBouillet, Philippe
dc.contributor.authorPuthalakath, Hamsa
dc.contributor.authorXu, Yeukang
dc.contributor.authorTarlinton, David M.
dc.contributor.authorStrasser, Andreas
dc.date.accessioned2015-12-07T22:32:49Z
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/1885/22972
dc.description.abstractDuring development, the stochastic process assembling the genes encoding antigen receptors invariably generates B and T lymphocytes that can recognize self-antigens. Several mechanisms have evolved to prevent the activation of these cells and the concomitant development of autoimmune disease. One such mechanism is the induction of apoptosis in developing or mature B cells by engagement of the B cell antigen receptor (BCR) in the absence of T cell help. Here we report that B lymphocytes lacking the pro-apoptotic Bcl-2 family member Bim are refractory to apoptosis induced by BCR ligation in vitro. The loss of Bim also inhibited deletion of autoreactive B cells in vivo in two transgenic systems of B cell tolerance, Bim loss prevented deletion of autoreactive B cells induced by soluble self-antigen and promoted accumulation of self-reactive B cells developing in the presence of membrane-bound self-antigen, although their numbers were considerably lower compared with antigen-free mice. Mechanistically, we determined that BCR ligation promoted interaction of Bim with Bcl-2, inhibiting its survival function. These findings demonstrate that Bim is a critical player in BCR-mediated apoptosis and in B lymphocyte deletion.
dc.publisherRockefeller University Press
dc.sourceJournal of Experimental Medicine
dc.subjectKeywords: autoantigen; B lymphocyte antigen; b lymphocyte antigen receptor; B lymphocyte receptor; BIM protein; cell protein; protein bcl 2; unclassified drug; animal cell; antigen recognition; apoptosis; article; autoimmunity; B lymphocyte; B lymphocyte deletion; Apoptosis; Autoimmunity; Gene knockout; Tolerance; Transgenic mice
dc.titleLoss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume198
dc.date.issued2003
local.identifier.absfor110200 - CARDIOVASCULAR MEDICINE AND HAEMATOLOGY
local.identifier.ariespublicationu4692404xPUB24
local.type.statusPublished Version
local.contributor.affiliationEnders, Anselm, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationBouillet, Philippe, The Walter and Eliza Hall Institute of Medical Research
local.contributor.affiliationPuthalakath, Hamsa, The Walter and Eliza Hall Institute of Medical Research
local.contributor.affiliationXu, Yeukang, The Walter and Eliza Hall Institute of Medical Research
local.contributor.affiliationTarlinton, David M., The Walter and Eliza Hall Institute of Medical Research
local.contributor.affiliationStrasser, Andreas, Walter and Eliza Hall Institute of Medical Research
local.description.embargo2037-12-31
local.bibliographicCitation.issue7
local.bibliographicCitation.startpage1119
local.bibliographicCitation.lastpage1126
local.identifier.doi10.1084/jem.20030411
dc.date.updated2015-12-07T10:24:18Z
local.identifier.scopusID2-s2.0-0141959215
CollectionsANU Research Publications

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