A thymus candidate in lampreys

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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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Figure 1: Tissue-specific expression of VLR and CDA genes in L. planeri larvae.
Figure 2: Characterization of the lamprey thymoid.
Figure 3: Stimulation does not affect cell proliferation and gene expression in the thymoid of P. marinus.
Figure 4: Selection of VLRA -expressing lymphocytes in the thymoid.

References

  1. 1

    Finstad, J. & Good, R. A. The evolution of the immune response. III. Immunologic responses in the lamprey. J. Exp. Med. 120, 1151–1168 (1964)

  2. 2

    Mayer, W. E. et al. Isolation and characterization of lymphocyte-like cells from a lamprey. Proc. Natl Acad. Sci. USA 99, 14350–14355 (2002)

  3. 3

    Pancer, Z. et al. Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey. Nature 430, 174–180 (2004)

  4. 4

    Pancer, Z. et al. Variable lymphocyte receptors in hagfish. Proc. Natl Acad. Sci. USA 102, 9224–9229 (2005)

  5. 5

    Guo, P. et al. Dual nature of the adaptive immune system in lampreys. Nature 459, 796–801 (2009)

  6. 6

    Alder, M. N. et al. Diversity and function of adaptive immune receptors in a jawless vertebrate. Science 310, 1970–1973 (2005)

  7. 7

    Cooper, M. D. & Alder, M. N. The evolution of adaptive immune systems. Cell 124, 815–822 (2006)

  8. 8

    Nagawa, F. et al. Antigen-receptor genes of the agnathan lamprey are assembled by a process involving copy choice. Nature Immunol. 8, 206–213 (2007)

  9. 9

    Rogozin, I. B. et al. Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase. Nature Immunol. 8, 647–656 (2007)

  10. 10

    Bajoghli, B. et al. Evolution of genetic networks underlying the emergence of thymopoiesis in vertebrates. Cell 138, 186–197 (2009)

  11. 11

    Boehm, T. & Bleul, C. C. The evolutionary history of lymphoid organs. Nature Immunol. 8, 131–135 (2007)

  12. 12

    Nehls, M. et al. Two genetically separable steps in the differentiation of thymic epithelium. Science 272, 886–889 (1996)

  13. 13

    Schaffer, J. Über die Thymusanlage bei Petromyzon planeri. Zweite vorläufige Mittheilung über den feineren Bau des Thymus. Sber. K. Akad. Wiss. 103, 149–156 (1894)

  14. 14

    Wallin, I. E. The relationships and histogenesis of thymus-like structures in ammocoetes. Am. J. Anat. 22, 127–167 (1917)

  15. 15

    Alder, M. N. et al. Antibody responses of variable lymphocyte receptors in the lamprey. Nature Immunol. 9, 319–327 (2008)

  16. 16

    Kishishita, N. et al. Regulation of antigen-receptor gene assembly in hagfish. EMBO Rep. 11, 126–132 (2010)

  17. 17

    Kasamatsu, J. et al. Identification of a third variable lymphocyte receptor in the lamprey. Proc. Natl Acad. Sci. USA 107, 14304–14308 (2010)

  18. 18

    Espina, V. et al. Laser-capture microdissection. Nature Protocols 1, 586–603 (2006)

  19. 19

    Bockman, D. E. & Cooper, M. D. Pinocytosis by epithelium associated with lymphoid follicles in the bursa of Fabricius, appendix, and Peyer's patches. An electron microscopic study. Am. J. Anat. 136, 455–477 (1973)

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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.

Author information

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.

Correspondence to Thomas 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) doi:10.1038/nature09655

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