A thymus candidate in lampreys (original) (raw)

Nature volume 470, pages 90–94 (2011)Cite this article

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Abstract

Immunologists and evolutionary biologists have been debating the nature of the immune system of jawless vertebrates—lampreys and hagfish—since the nineteenth century. In the past 50 years, these fish were shown to have antibody-like responses and the capacity to reject allografts1 but were found to lack the immunoglobulin-based adaptive immune system of jawed vertebrates2. Recent work has shown that lampreys have lymphocytes that instead express somatically diversified antigen receptors that contain leucine-rich-repeats, termed variable lymphocyte receptors (VLRs)3,4, and that the type of VLR expressed is specific to the lymphocyte lineage: T-like lymphocytes express type A VLR (VLRA) genes, and B-like lymphocytes express VLRB genes5. These clonally diverse anticipatory antigen receptors are assembled from incomplete genomic fragments by gene conversion6,7,8,9, which is thought to be initiated by either of two genes encoding cytosine deaminase9, cytosine deaminase 1 (CDA1) in T-like cells and CDA2 in B-like cells5. It is unknown whether jawless fish, like jawed vertebrates, have dedicated primary lymphoid organs, such as the thymus, where the development and selection of lymphocytes takes place10,11. Here we identify discrete thymus-like lympho-epithelial structures, termed thymoids, in the tips of the gill filaments and the neighbouring secondary lamellae (both within the gill basket) of lamprey larvae. Only in the thymoids was expression of the orthologue of the gene encoding forkhead box N1 (FOXN1)10, a marker of the thymopoietic microenvironment in jawed vertebrates12, accompanied by expression of CDA1 and VLRA. This expression pattern was unaffected by immunization of lampreys or by stimulation with a T-cell mitogen. Non-functional VLRA gene assemblies were found frequently in the thymoids but not elsewhere, further implicating the thymoid as the site of development of T-like cells in lampreys. These findings suggest that the similarities underlying the dual nature of the adaptive immune systems in the two sister groups of vertebrates extend to primary lymphoid organs.

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Acknowledgements

We thank C. Happe and M. Held for technical help, C. L. Turnbough Jr for providing B. anthracis spores and exosporia, and the Emory University School of Medicine core facility for flow cytometry for cell-sorting services. This work was supported by the Max Planck Society, the Deutsche Forschungsgemeinschaft, the National Institutes of Health and the Georgia Research Alliance.

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Authors and Affiliations

  1. Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, D-79108 Freiburg, Germany,
    Baubak Bajoghli, Narges Aghaallaei, Christine Strohmeier, Michael Schorpp & Thomas Boehm
  2. Emory Vaccine Center, 954 Gatewood Road, Atlanta, 30329, Georgia, USA
    Peng Guo, Masayuki Hirano, Nathanael McCurley & Max D. Cooper
  3. Department of Pathology and Laboratory Medicine, Emory University, 1462 Clifton Road North-East, Atlanta, Georgia 30322, USA,
    Peng Guo, Masayuki Hirano, Nathanael McCurley & Max D. Cooper
  4. Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, 30912, Georgia, USA
    Dale E. Bockman

Authors

  1. Baubak Bajoghli
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  2. Peng Guo
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  3. Narges Aghaallaei
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  4. Masayuki Hirano
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  5. Christine Strohmeier
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  6. Nathanael McCurley
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  7. Dale E. Bockman
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  8. Michael Schorpp
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  9. Max D. Cooper
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  10. Thomas Boehm
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Contributions

B.B., P.G., N.A., M.H., C.S., N.M., D.E.B., M.S., M.D.C. and T.B. designed the experiments, performed the research, analysed the data and wrote the manuscript.

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Correspondence toThomas Boehm.

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The authors declare no competing financial interests.

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Bajoghli, B., Guo, P., Aghaallaei, N. et al. A thymus candidate in lampreys.Nature 470, 90–94 (2011). https://doi.org/10.1038/nature09655

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Editorial Summary

The lamprey's thymoid and vertebrate immunity

The immune system of lampreys — jawless fish with roots in the early separation of the vertebrates into jawed and jawless lines — is of particular interest to evolutionary biologists. Much has been made of the differences between the 'alternative' immune system in the lamprey and that of today's jawed vertebrates, but the recent discovery that lampreys have lymphocytes resembling B and T cells, which are central to the adaptive immune response of the jawed vertebrates, puts more emphasis on the search for similarities. Histological surveys of lampreys have failed to reveal an organ equivalent to the mammalian thymus, the organ that generates the development of T lymphocytes. Now, gene expression analysis reveals previously unrecognized thymus-like structures — termed thymoids — at the tips of gill filaments of lamprey larvae. This suggests that the common ancestor of the jawed and jawless vertebrates may have had not only T- and B-like lymphocytes, but also anatomically distinct tissues for their development.