Determinants of Intrathymic T-Cell Fate Decisions (A01)

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The thymus harbors besides dendritic cells and medullary thymic epithelial cells substantial numbers of B cells; however, their role in central T cell tolerance induction is only poorly understood. In line with the notion that B cells significantly shape the CD4 T cell compartment, we recently identified a substantial number of TCRs in the conventional T cell (Tconv) repertoire of B-cell-deficient mice that are absent from the Tconv repertoire in B-cell-sufficient mice. In the third funding period, we will investigate how (deletion versus Treg cell induction) and to which extent thymic B cells shape the CD4 T cell repertoire and whether by-passing the B-cell-mediated thymic checkpoint results in perturbations of immune homeostasis, for instance ‘misguided’ germinal center reactions or even overt autoimmunity.