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A Role For Intrathymic B Cells in the Generation of Natural Regulatory T Cells

Walters, Stacey N; Webster, Kylie E; Daley, Stephen; Grey, Shane T

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B cells inhabit the normal human thymus, suggesting a role in T cell selection. In this study, we report that B cells can modulate thymic production of CD4+ Foxp3+ T cells (regulatory T cells [Tregs]). Mice with transgenic expression of BAFF (BAFF-Tg) harbor increased numbers of Helios+Foxp3+ thymic Tregs and, similar to some human autoimmune conditions, also exhibit increased numbers of B cells colonizing the thymus. Distinct intrathymic B cell subpopulations were identified, namely B220+,...[Show more]

dc.contributor.authorWalters, Stacey N
dc.contributor.authorWebster, Kylie E
dc.contributor.authorDaley, Stephen
dc.contributor.authorGrey, Shane T
dc.date.accessioned2015-12-13T22:27:23Z
dc.identifier.issn0022-1767
dc.identifier.urihttp://hdl.handle.net/1885/73926
dc.description.abstractB cells inhabit the normal human thymus, suggesting a role in T cell selection. In this study, we report that B cells can modulate thymic production of CD4+ Foxp3+ T cells (regulatory T cells [Tregs]). Mice with transgenic expression of BAFF (BAFF-Tg) harbor increased numbers of Helios+Foxp3+ thymic Tregs and, similar to some human autoimmune conditions, also exhibit increased numbers of B cells colonizing the thymus. Distinct intrathymic B cell subpopulations were identified, namely B220+, IgM+, CD23hi, CD21int cells; B220+, IgM+, CD23lo, CD21lo cells; and a population of B220+, IgM+, CD23lo, CD21hi cells. Anatomically, CD19+ B cells accumulated in the thymic medulla region juxtaposed to Foxp3+ T cells. These intrathymic B cells engender Tregs. Indeed, thymic Treg development was diminished in both B cell-deficient BAFF-Tg chimeras, but also B cell- deficient wild-type chimeras. B cell Ag capture and presentation are critical in vivo events for Treg development. In the absence of B cell surface MHC class II expression, thymic expansion of BAFF-Tg Tregs was lost. Further to this, expansion of Tregs did not occur in BAFF-Tg/Ig hen egg lysozyme BCR chimeras, demonstrating a requirement for Ag specificity. Thus, we present a mechanism whereby intrathymic B cells, through the provision of cognate help, contribute to the shaping of the Treg repertoire.
dc.publisherAmerican Association of Immunologists
dc.sourceJournal of Immunology
dc.titleA Role For Intrathymic B Cells in the Generation of Natural Regulatory T Cells
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume193
dc.date.issued2014
local.identifier.absfor110700 - IMMUNOLOGY
local.identifier.ariespublicationU3488905xPUB3891
local.type.statusPublished Version
local.contributor.affiliationWalters, Stacey N, Garvan Institute of Medical Research
local.contributor.affiliationWebster, Kylie E, Garvan Institute of Medical Research
local.contributor.affiliationDaley, Stephen, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationGrey, Shane T, Garvan Institute of Medical Research
local.description.embargo2037-12-31
local.bibliographicCitation.issue1
local.bibliographicCitation.startpage170
local.bibliographicCitation.lastpage176
local.identifier.doi10.4049/jimmunol.1302519
dc.date.updated2015-12-11T08:31:06Z
local.identifier.scopusID2-s2.0-84903625200
local.identifier.thomsonID000338438900022
CollectionsANU Research Publications

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