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Updated: Jun 26, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry
Published on: October 8, 2012
Sustained expression of pre-TCR induced beta-catenin in post-beta-selection thymocytes blocks T cell development
Mai Xu1, Archna Sharma, M Zulfiquer Hossain
1Lymphocyte Development Unit, Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Abstract:
Pre-TCR and IL-7R signals regulate beta-selection of thymocytes and then must be down-regulated for further development. However, the molecular events that control down-regulation remain unknown. We and others have previously shown that beta-catenin in cooperation with TCF regulates beta-selection. In this paper, we demonstrate that beta-catenin expression is stringently regulated by intrathymic signals, it is expressed at the highest levels in the pre-TCR signaled thymocytes, and is down-regulated in post-beta-selection thymocytes. Pre-TCR-induced beta-catenin regulates initial stages of pre-TCR signaling including expression of early growth response (Egr) genes but must be down-regulated to express RORgammat, which is essential for maturation to the CD4+CD8+ double positive (DP) stage. Sustained expression of beta-catenin results in the generation of IL-7R-, Egr-, and TGFbeta-expressing pre-DP thymocytes that are blocked in development. These data are consistent with a model in which post-beta-selection, pre-TCR-induced beta-catenin expression must return to background levels for efficient transition to the DP stage.
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