A Role For Intrathymic B Cells in the Generation of Natural Regulatory T Cells
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Walters, Stacey N; Webster, Kylie E; Daley, Stephen; Grey, Shane T
Description
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.author | Walters, Stacey N | |
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dc.contributor.author | Webster, Kylie E | |
dc.contributor.author | Daley, Stephen | |
dc.contributor.author | Grey, Shane T | |
dc.date.accessioned | 2015-12-13T22:27:23Z | |
dc.identifier.issn | 0022-1767 | |
dc.identifier.uri | http://hdl.handle.net/1885/73926 | |
dc.description.abstract | 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+, 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.publisher | American Association of Immunologists | |
dc.source | Journal of Immunology | |
dc.title | A Role For Intrathymic B Cells in the Generation of Natural Regulatory T Cells | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 193 | |
dc.date.issued | 2014 | |
local.identifier.absfor | 110700 - IMMUNOLOGY | |
local.identifier.ariespublication | U3488905xPUB3891 | |
local.type.status | Published Version | |
local.contributor.affiliation | Walters, Stacey N, Garvan Institute of Medical Research | |
local.contributor.affiliation | Webster, Kylie E, Garvan Institute of Medical Research | |
local.contributor.affiliation | Daley, Stephen, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Grey, Shane T, Garvan Institute of Medical Research | |
local.description.embargo | 2037-12-31 | |
local.bibliographicCitation.issue | 1 | |
local.bibliographicCitation.startpage | 170 | |
local.bibliographicCitation.lastpage | 176 | |
local.identifier.doi | 10.4049/jimmunol.1302519 | |
dc.date.updated | 2015-12-11T08:31:06Z | |
local.identifier.scopusID | 2-s2.0-84903625200 | |
local.identifier.thomsonID | 000338438900022 | |
Collections | ANU Research Publications |
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