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Bcl11b is required for differentiation and survival of αβ T lymphocytes

Nature Immunology volume 4, pages 533–539 (2003)Cite this article

Abstract

The gene Bcl11b, which encodes zinc finger proteins, and its paralog, Bcl11a, are associated with immune-system malignancies. We have generated Bcl11b-deficient mice that show a block at the CD4−CD8− double-negative stage of thymocyte development without any impairment in cells of B- or γδ T cell lineages. The Bcl11b−/− thymocytes showed unsuccessful recombination of Vβ to Dβ and lacked the pre–T cell receptor (TCR) complex on the cell surface, owing to the absence of Tcrb mRNA expression. In addition, we saw profound apoptosis in the thymus of neonatal Bcl11b−/− mice. These results suggest that Bcl11b is a key regulator of both differentiation and survival during thymocyte development.

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Figure 1: Bcl11b transcripts and proteins in the thymus.
Figure 2: Targeting strategy for Bcl11b knockout mice.
Figure 3: Developmental arrest of thymocytes in Bcl11b−/− mice.
Figure 4: Reconstitution of B and γδ T cells in SCID mice transferred with fetal liver cells.
Figure 5: Apoptosis assay of thymus.
Figure 6: Expression of apoptosis-related proteins.

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Acknowledgements

This work was supported by a Grant-in-Aid for scientific research from the Ministry of Education, Science, Culture and Sports and by a Health Science Research Grant from the Ministry of Health, Labor and Welfare of Japan. We thank K. Toba for cell cycle analysis by flow cytometry, and A. Balmain, K. Hirokawa, T. Abo, M. Naito and A. Shimizu for helpful comments.

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Author notes

  1. Shinichi Aizawa

    Present address: Riken Institute, Minatojima Minamimachi 2-2-3, Chuou-ku, Koube, Hyougo, 650-0047, Japan

Authors and Affiliations

  1. Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata, 951-8122, Japan

    Yuichi Wakabayashi, Jun Inoue, Jun Sakata, Yukio Mishima & Ryo Kominami

  2. Division of Cellular and Molecular Immunology, Center of Molecular Biosciences, University of the Ryukyus, Nishihara Senbaru 1, Okinawa, 903-0213, Japan

    Hisami Watanabe

  3. Institute Molecular Embryology and Genetics, Kumamoto University, Honjou 2-2-1, Kumamoto, 860-0811, Japan

    Naoki Takeda & Shinichi Aizawa

  4. Department of Cellular Function, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata, 951-8122, Japan

    Jiro Hitomi & Takashi Yamamoto

  5. Department of Pathology and Immunology, Tokyo Medical and Dental University Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8519, Japan

    Masanori Utsuyama

  6. Radiation Biology Center, Kyoto University, Yoshida-Konoecho, Sakyou-Ku, Kyoto, 606-8315, Japan

    Ohtsura Niwa

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  1. Yuichi Wakabayashi
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Correspondence to Ryo Kominami.

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Wakabayashi, Y., Watanabe, H., Inoue, J. et al. Bcl11b is required for differentiation and survival of αβ T lymphocytes. Nat Immunol 4, 533–539 (2003). https://doi.org/10.1038/ni927

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