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A role for intrathymic B cells in the generation of natural regulatory T cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Jul 01; Vol. 193 (1), pp. 170-6. Date of Electronic Publication: 2014 May 28. - Publication Year :
- 2014
-
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+, CD23(hi), CD21(int) cells; B220+, IgM+, CD23(lo), CD21(lo) cells; and a population of B220+, IgM+, CD23(lo), CD21(hi) 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.<br /> (Copyright © 2014 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Antigens genetics
Antigens immunology
Antigens, Differentiation genetics
Antigens, Differentiation immunology
B-Cell Activating Factor genetics
B-Cell Activating Factor immunology
B-Lymphocytes cytology
Gene Expression Regulation genetics
Gene Expression Regulation immunology
Histocompatibility Antigens Class II genetics
Histocompatibility Antigens Class II immunology
Humans
Mice
Mice, Inbred BALB C
Mice, Knockout
Receptors, Antigen, B-Cell genetics
Receptors, Antigen, B-Cell immunology
T-Lymphocytes, Regulatory cytology
Thymus Gland cytology
B-Lymphocytes immunology
T-Lymphocytes, Regulatory immunology
Thymus Gland immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 193
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 24872190
- Full Text :
- https://doi.org/10.4049/jimmunol.1302519