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Stage-specific functions of E-proteins at the β-selection and T-cell receptor checkpoints during thymocyte development

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Abstract

The E-protein transcription factors E2A and HEB function in a lineage- and stage-specific manner to orchestrate many critical events throughout lymphocyte development. The function of E-proteins in both B- and T-lymphocyte development has been extensively studied through the use of single-gene knockout animals. Unlike B cells, which rely primarily on E2A alone, T cells are regulated by the combinatorial expression of both E2A and HEB. Therefore, many of the roles of E-proteins during T-cell development may be masked in single-gene knockout studies due to the compensatory function of E2A and HEB. More recently, our laboratory has established double-conditional knockout models to eliminate both E2A and HEB in a stage-specific manner throughout T-cell development. These models, in combination with other complimentary genetic approaches, have identified new E-protein functions at each of the two major T-cell developmental checkpoints. Here, we will discuss how E-proteins function to regulate the expression of T-cell receptor components and cell cycle at the β-selection checkpoint, and how they control positive selection, survival, and lineage-specific gene expression at the subsequent T-cell receptor checkpoint.

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Acknowledgments

Work in the authors’ laboratory was supported by NIH grants to Y.Z.

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  1. Department of Immunology, Duke University Medical Center, Box 3010, Durham, NC, 27710, USA

    Mary Elizabeth Jones & Yuan Zhuang

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  1. Mary Elizabeth Jones
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Jones, M.E., Zhuang, Y. Stage-specific functions of E-proteins at the β-selection and T-cell receptor checkpoints during thymocyte development. Immunol Res 49, 202–215 (2011). https://doi.org/10.1007/s12026-010-8182-x

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