BCL11B is required for positive selection and survival of double-positive thymocytes

Diana I. Albu, Dongyun Feng, Debarati Bhattacharya, Nancy A. Jenkins, Neal G. Copeland, Pentao Liu, Dorina Avram

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Transcriptional control of gene expression in double-positive (DP) thymocytes remains poorly understood. We show that the transcription factor BCL11B plays a critical role in DP thymocytes by controlling positive selection of both CD4 and CD8 lineages. BCL11B-deficient DP thymocytes rearrange T cell receptor (TCR) α; however, they display impaired proximal TCR signaling and attenuated extracellular signal-regulated kinase phosphorylation and calcium flux, which are all required for initiation of positive selection. Further, provision of transgenic TCRs did not improve positive selection of BCL11Bdeficient DP thymocytes. BCL11B-deficient DP thymocytes have altered expression of genes with a role in positive selection, TCR signaling, and other signaling pathways intersecting the TCR, which may account for the defect. BCL11B-deficient DP thymocytes also presented increased susceptibility to spontaneous apoptosis associated with high levels of cleaved caspase-3 and an altered balance of proapoptotic/prosurvival factors. This latter susceptibility was manifested even in the absence of TCR signaling and was only partially rescued by provision of the BCL2 transgene, indicating that control of DP thymocyte survival by BCL11B is nonredundant and, at least in part, independent of BCL2 prosurvival factors. JEM

Original languageEnglish (US)
Pages (from-to)3003-3015
Number of pages13
JournalJournal of Experimental Medicine
Volume204
Issue number12
DOIs
StatePublished - Nov 26 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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