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

Tomoyoshi Yamano, Jelena Nedjic, Maria Hinterberger, Madlen Steinert, Sandra Koser, Sheena Pinto, Norbert Gerdes, Esther Lutgens, Naozumi Ishimaru, Meinrad Busslinger, Benedikt Brors, Bruno Kyewski, Ludger Klein

Research output: Contribution to journalArticlepeer-review


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 languageEnglish (US)
Pages (from-to)1048-1061
Number of pages14
Issue number6
StatePublished - Jun 16 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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