A role for intrathymic B cells in the generation of natural regulatory T cells
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.
|ISBN||1550-6606 (Electronic) 0022-1767 (Linking)|
|Authors||Walters, S. N. ; Webster, K. E. ; Daley, S. ; Grey, S. T.;|
|Responsible Garvan Author|
|Publisher Name||JOURNAL OF IMMUNOLOGY|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/24872190|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/12480|