Intrathymic B cell licensing for Aire expression and T cell tolerance induction

Thymic antigen presenting cells (APCs) use diverse, cell type-specific strategies of self- antigen expression and presentation to co-operatively impose central tolerance. We found that intrathymic expression of Aire is not limited to medullary thymic epithelial cells, but also occurs in thymic B cells. Aire expression in B cells results from an intrathymic ‘licensing’ process that is triggered by a cross-talk with immature CD4+ thymocytes and which also elicits up-regulation of MHCII, induction of CD80 and immunoglobulin class-switching. A neo- antigen whose expression mimicked ‘licensing-associated’ self-antigen induction was directly presented by immigrating peripheral B cells for negative selection. Thus, autoreactivity within the nascent T cell repertoire fuels a tolerogenic feed forward loop that endows thymic B cells with potent APC features.