Journal
IMMUNITY
Volume 42, Issue 6, Pages 1048-1061Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2015.05.013
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Funding
- Deutsche Forschungsgemeinschaft (IRTG) [KL 1228/5-1, SFB 1054]
- Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship
- DFG grant [LK 1228/6-1]
- Marie Curie postdoctoral fellowship from European Union
- European Research Council (ERC-AdG)
- Grants-in-Aid for Scientific Research [15K15676] Funding Source: KAKEN
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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 in thymic B cells coincided with major histocompatibility class II (MHCII) and CD80 upregulation and immunoglobulin 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 T cell repertoire fuels a feed forward loop that endows thymic B cells with tolerogenic features.
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