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Conditioned deletion of ephrinB1 and/or ephrinB2 in either thymocytes or thymic epithelial cells alters the organization of thymic medulla and favors the appearance of thymic epithelial cysts

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Abstract

Our understanding about medullary compartment, its niches composition and formation is still limited. Previous studies using EphB2 and/or EphB3 knockout mice showed an abnormal thymic development that affects mainly to the epithelial component, including the cortex/medulla distribution, thymic epithelial cell (TEC) morphology and different epithelial-specific marker expression. We have already demonstrated that the lack of ephrinB1 and/or ephrinB2, either on thymocytes or on TECs, alters the cell intermingling processes necessary for thymus organization and affect cortical TEC subpopulations. In the present work, we have used the Cre–LoxP model to selectively delete ephrinB1 and/or ephrinB2 in thymocytes (EfnB1thy/thy, EfnB2thy/thy, EfnB1thy/thyEfnB2thy/thy mice) or TECs (EfnB1tec/tec, EfnB2tec/tec, EfnB1tec/tecEfnB2tec/tec mice) and have analyzed their role on the medullary compartment. In all the studied mutants, medullary areas are smaller and more compact than in the wt thymuses. In most of them, we observe abundant big cysts and a higher proportion of UEAhiMTS10− cells than in wt mice, which are often forming small cysts. On EfnB1tec/tecEfnB2tec/tec, changes affecting organ size and medullary compartment start at perinatal stage. Our data shed some light on knowledge about wt medulla histological structure and cysts meaning and formation process and on the role played by ephrinB in them.

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Acknowledgments

This work was supported by grants BFU2007-65520 and BFU2010-18250 from Spanish Ministry of Education and Science; RD06/0010/0003 and RD12/0019/0007 from Spanish Ministry of Health and Consume, and S-BIO/0204/2006 and R74/91-05552/08 from the Regional Government of Madrid. We thank Dr. D.J. Anderson (California Institute of Technology, Pasadena, California) for providing C57BL/6-EfnB1LoxP/LoxP mice, Dr. J.J. Takeda and the Center for Animal Resources and Development of the Kumamoto University (Japan) for the gift of C57BL/6-Tg(K5-Cre) Jt strain and Dr. R. Boyd, (Monash University, Melbourne, Australia) for the donation of the MTS10 and MTS20 antibodies. We would like to also thank to the “Developmental Studies Hybridoma Bank” of Iowa University for supplying the anti-K8 keratin antibody and to the Cytometry and Fluorescence Microscopy Centre at Complutense University of Madrid for the use of its facilities and technical assistance.

Conflict of interest

The authors declare no commercial or financial conflict of interest.

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Authors and Affiliations

  1. Cytometry and Fluorescence Microscopy Centre, Complutense University of Madrid, Madrid, Spain

    Teresa Cejalvo & Juan J. Munoz

  2. Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain

    Esther Tobajas, David Alfaro, Javier García-Ceca & Agustín Zapata

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  1. Teresa Cejalvo
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  2. Juan J. Munoz
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  3. Esther Tobajas
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  4. David Alfaro
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  5. Javier García-Ceca
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  6. Agustín Zapata
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Correspondence to Agustín Zapata.

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Teresa Cejalvo and Juan J. Munoz have contributed equally to this study.

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Cejalvo, T., Munoz, J.J., Tobajas, E. et al. Conditioned deletion of ephrinB1 and/or ephrinB2 in either thymocytes or thymic epithelial cells alters the organization of thymic medulla and favors the appearance of thymic epithelial cysts. Histochem Cell Biol 143, 517–529 (2015). https://doi.org/10.1007/s00418-014-1296-9

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