Abstract
Thymic antigen-presenting cells (APCs) such as dendritic cells and medullary thymic epithelial cells (mTECs) use distinct strategies of self-antigen expression and presentation to mediate central tolerance. The thymus also harbors B cells; whether they also display unique tolerogenic features and how they genealogically relate to peripheral B cells is unclear. Here, we found that Aire is expressed in thymic but not peripheral B cells. Aire expression inthymic B cells coincided with major histocompatibility class II (MHCII) and CD80 upregulation andimmunoglobulin class-switching. These features were recapitulated upon immigration of naive peripheral B cells into the thymus, whereby this intrathymic licensing required CD40 signaling in the context of cognate interactions with autoreactive CD4+ thymocytes. Moreover, a licensing-dependent neo-antigen selectively upregulated in immigrating B cells mediated negative selection through direct presentation. Thus, autoreactivity within the nascent Tcell repertoire fuels a feed forward loop that endows thymic B cells with tolerogenic features.
Original language | English (US) |
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Pages (from-to) | 1048-1061 |
Number of pages | 14 |
Journal | Immunity |
Volume | 42 |
Issue number | 6 |
DOIs | |
State | Published - Jun 16 2015 |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases