Identification of a genomic enhancer that enforces proper apoptosis induction in thymic negative selection.

ABSTRACT: During thymic negative selection, autoreactive thymocytes carrying T cell receptor (TCR) with overtly strong affinity to self-MHC/self-peptide are removed by Bim-dependent apoptosis, but how Bim is specifically regulated to link TCR activation and apoptosis induction is unclear. Here we identify a murine T cell-specific genomic enhancer E^{BAB (Bub1-Acoxl-Bim)}, whose deletion leads to accumulation of thymocytes expressing high affinity TCRs. Consistently, E^BAB knockout mice have defective negative selection and fail to delete autoreactive thymocytes in various settings, with this defect accompanied by reduced Bim expression and apoptosis induction. By contrast, E^BAB is dispensable for maintaining peripheral T cell homeostasis via Bim-dependent pathways. Our d

SUBMITTER: Hojo MA 

PROVIDER: S-EPMC6565714 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature