Determinants of Intrathymic T-Cell Fate Decisions (A01)

除了树突状细胞和胸腺髓质上皮细胞外，胸腺还含有大量的B细胞;然而，它们在中枢T细胞耐受诱导中的作用知之甚少。与B细胞显著地形成CD 4 T细胞区室的概念一致，我们最近在B细胞缺陷小鼠的常规T细胞（Tconv）库中鉴定了大量TCR，其在B细胞充足小鼠的Tconv库中不存在。在第三个资助期，我们将研究胸腺B细胞如何（缺失与Treg细胞诱导）以及在多大程度上塑造CD 4 T细胞库，以及绕过B细胞介导的胸腺检查点是否会导致免疫稳态的扰动，例如“误导”的生发中心反应，甚至是明显的自身免疫。

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.