Institute for Immunology, Biomedical Center (BMC)
Role of thymic B cells in central T cell tolerance
Role of thymic B cells in central T cell tolerance
Tolerance to self-antigens is a fundamental property of the immune system. During central tolerance induction in the thymus, autoreactive T cells are either eliminated or diverted into the regulatory T cell lineage. Both processes are dependent on the presentation of self-antigens by thymic antigen presenting cells (APCs). Commonly, dendritic cells and medullary thymic epithelial cells are believed to represent the key APCs for central T cell tolerance (1). The thymus also harbors a distinct population of B cells, raising the possibility that thymic B cells serve a non-redundant APC function in central T cell tolerance induction (2). We have recently tested this hypothesis through large scale comparisons of the TCR composition of ‘normally’ selected T cell repertoires versus repertoires selected in the absence of B cells, Dendritic cells, or both. This identified a surprisingly large cohort of TCRs whose negative selection under physiological circumstances crucially requires thymic B cells. In future work, we aim to elucidate the antigen specificities of such “B-cell-deleted” clones. Moreover, we will re-express selected candidate TCRs in TCR transgenic mice to define their precise selection modalities, and to determine the (pathological?) consequences of bypassing the B-cell-mediated tolerance checkpoint.
1. Petrozziello E., Klein L. (2025) Antigen presentation for cental tolerance induction. Nature Reviews Immunology, 25(1): 57-72.
2. Yamano T., … and Klein L. (2015) Thymic B cells are licensed to present self antigens for central T cell tolerance induction. Immunity, 42(6): 1048-1061.