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Defining the specific physiological requirements for c-Myc in T cell development

Nature Immunology volume 2, pages 307–315 (2001)Cite this article

Abstract

c-Myc is associated with cell growth and cycling in many tissues and its deregulated expression is causally implicated in cancer, particularly lymphomagenesis. However, the contribution of c-Myc to lymphocyte development is unresolved. We show here that the formation of normal lymphocytes by c-Myc−/− cells is selectively defective. c-Myc−/− cells are inefficient, in an age-dependent manner, at populating the thymus, and subsequent thymocyte maturation is ineffective: they fail to grow and proliferate normally at the late double-negative (DN) CD4−CD8− stage. Because N-Myc expression in thymocytes usually declines at the late DN stage, these results confirm that the nonredundant contributions of Myc family members to development are related to their distinct patterns of developmental gene expression.

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Figure 1: Development of c-Myc−/− and c-Myc+/− ES cells.
Figure 2: c-Myc−/− cells do not efficiently form lymphocytes in RAG-1−/− chimeras.
Figure 3: c-Myc−/− cells do not efficiently complete thymocyte differentiation in adult RAG-1−/− chimeras.
Figure 4: c-Myc−/− cells do not contribute effectively to the bone marrow.
Figure 5: Analysis of c-Myc+/− and c-Myc−/− fetal thymocytes at E16.5.
Figure 6: Maturation of c-Myc−/− thymocytes.
Figure 7: c-Myc and N-Myc gene expression in C57BL/6J thymocyte subsets.

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Acknowledgements

We thank D. Barber, R. Carbone, J. Cridland, S. Maher, J. McGrath, D. Schatz, T. Taylor, R. Tigelaar, W. Turnbull, E. Hoffman, L. Passoni, S. John, S. Roberts, M. Owen, J. Lewis, S. Creighton and, particularly, R. Sullo. Supported by the Wellcome Trust and by National Institutes of Health grant GM37759 (to A. C. H.). N. C. D. is supported by MSTP.

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Authors and Affiliations

  1. Department of Molecular Cell and Developmental Biology, Yale University, New Haven, 06520, CT, USA

    Nataki C. Douglas & Adrian C. Hayday

  2. Department of Pediatrics, Yale University, New Haven, 06520, CT, USA

    Harris Jacobs

  3. Section of Immunobiology, Yale University, New Haven, 06520, CT, USA

    Alfred L. M. Bothwell & Adrian C. Hayday

  4. Peter Gorer Department of Immunobiology, Guy's King's St Thomas' Medical School, Guy's Hospital, London, SE1 9RT, UK

    Adrian C. Hayday

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  1. Nataki C. Douglas
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Corresponding author

Correspondence to Adrian C. Hayday.

Supplementary information

Web Table 1.

TCRβ and TCRδ gene rearrangements in thymocytes of c-Myc−/− RAG-1−/− chimeras (DOC 32 kb)

Web Table 2.

TCRγ gene rearrangements in thymocytes of c-Myc−/−RAG-1−/− chimeras, arranged according to germline contributions from V and J segments and presumed template-independent N or P nucleotides (DOC 21 kb)

Web Table 3.

The frequencies of in-frame TCRβ gene rearrangements (DOC 19 kb)

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Douglas, N., Jacobs, H., Bothwell, A. et al. Defining the specific physiological requirements for c-Myc in T cell development. Nat Immunol 2, 307–315 (2001). https://doi.org/10.1038/86308

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