Article,

Thymic B Cells Are Licensed to Present Self Antigens for Central T Cell Tolerance Induction

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Immunity, 42 (6): 1048 - 1061 (2015)
DOI: http://dx.doi.org/10.1016/j.immuni.2015.05.013

Abstract

Summary 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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