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The evolutionary history of lymphoid organs

Nature Immunology volume 8, pages 131–135 (2007)Cite this article

Abstract

Lymphoid organs are important regulators of lymphocyte development and immune responses. During vertebrate evolution, primary lymphoid organs appeared earlier than secondary lymphoid organs. Among the sites of primary lymphopoiesis during evolution and ontogeny, those for B cell differentiation have differed considerably, although they often have had myelolymphatic characteristics. In contrast, only a single site for T cell differentiation has occurred, exclusively the thymus. Based on those observations and the known features of variable-diversity-joining gene recombination, we propose a model for the successive specification of different lymphocyte lineages during vertebrate evolution. According to our model, T cells were the first lymphocytes to acquire variable-diversity-joining–type receptors, and the thymus was the first lymphoid organ to evolve in vertebrates to deal with potentially autoreactive, somatically diversified T cell receptors.

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Figure 1: Evolution of lymphocyte specification.
Figure 2: Evolutionary origins of VDJ recombination.

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References

  1. Porter, R. The Greatest Benefit to Mankind: A Medical History of Humanity from Antiquity to the Present (Harper-Collins, New York, 1997).

    Google Scholar 

  2. Miller, J.F. Immunological function of the thymus. Lancet 2, 748–749 (1961).

    Article  CAS  Google Scholar 

  3. Le Douarin, N. The microenvironment of T and B lymphocyte differentiation in avian embryos. Curr. Top. Dev. Biol. 20, 291–313 (1986).

    Article  CAS  Google Scholar 

  4. Tonegawa, S. Somatic generation of antibody diversity. Nature 302, 575–581 (1983).

    Article  CAS  Google Scholar 

  5. Pancer, Z. & Cooper, M.D. The evolution of adaptive immunity. Annu. Rev. Immunol. 24, 497–518 (2006).

    Article  CAS  Google Scholar 

  6. Watson, F.L. et al. Extensive diversity of Ig-superfamily proteins in the immune system of insects. Science 18, 1826–1827 (2005).

    Google Scholar 

  7. Royet, J., Reichhart, J.M. & Hoffmann, J.A. Sensing and signaling during infection in Drosophila. Curr. Opin. Immunol. 17, 11–17 (2005).

    Article  CAS  Google Scholar 

  8. Dong, Y., Taylor, H.E. & Dimopoulos, G. AgDscam, a hypervariable immunoglobulin domain-containing receptor of the Anopheles gambiae innate immune system. PLoS Biol. 4, e229 (2006).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  10. Davis, M.M. & Bjorkman, P.J. T-cell antigen receptor genes and T-cell recognition. Nature 334, 395–402 (1988).

    Article  CAS  Google Scholar 

  11. Boehm, T. Quality control in self/nonself discrimination. Cell 125, 845–858 (2006).

    Article  CAS  Google Scholar 

  12. Medzhitov, R. & Janeway, C.A., Jr. Decoding the patterns of self and nonself by the innate immune system. Science 296, 298–300 (2002).

    Article  CAS  Google Scholar 

  13. Meylan, E., Tschopp, J. & Karin, M. Intracellular pattern recognition receptors in the host response. Nature 442, 39–44 (2006).

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  16. Cannon, J.P., Haire, R.N., Rast, J.P. & Litman, G.W. The phylogenetic origins of the antigen-binding receptors and somatic diversification mechanisms. Immunol. Rev. 200, 12–22 (2004).

    Article  CAS  Google Scholar 

  17. Kondo, M., Scherer, D.C., King, A.G., Manz, M.G. & Weissman, I.L. Lymphocyte development from hematopoietic stem cells. Curr. Opin. Genet. Dev. 11, 520–526 (2001).

    Article  CAS  Google Scholar 

  18. Hardy, R.R. & Hayakawa, K. B cell development pathways. Annu. Rev. Immunol. 19, 595–621 (2001).

    Article  CAS  Google Scholar 

  19. Schwarz, B.A. & Bhandoola, A. Trafficking from the bone marrow to the thymus: a prerequisite for thymopoiesis. Immunol. Rev. 209, 47–57 (2006).

    Article  Google Scholar 

  20. Boehm, T. & Bleul, C.C. Thymus-homing precursors and the thymic microenvironment. Trends Immunol. 27, 477–484 (2006).

    Article  CAS  Google Scholar 

  21. Du Pasquier, L. Ontogeny of the immune response in cold-blooded vertebrates. Curr. Top. Microbiol. Immunol. 61, 37–88 (1973).

    CAS  PubMed  Google Scholar 

  22. Knight, K.L. & Crane, M.A. Generating the antibody repertoire in rabbit. Adv. Immunol. 56, 179–218 (1994).

    Article  CAS  Google Scholar 

  23. Tagaya, H. et al. Intramedullary and extramedullary B lymphopoiesis in osteopetrotic mice. Blood 95, 3363–3370 (2000).

    CAS  PubMed  Google Scholar 

  24. Li, J. et al. B lymphocytes from early vertebrates have potent phagocytic and microbicidal abilities. Nat. Immunol. 7, 1116–1124 (2006).

    Article  CAS  Google Scholar 

  25. Cumano, A., Paige, C.J., Iscove, N.N. & Brady, G. Bipotential precursors of B cells and macrophages in murine fetal liver. Nature 356, 612–615 (1992).

    Article  CAS  Google Scholar 

  26. Montecino-Rodriguez, E., Leathers, H. & Dorshkind, K. Bipotential B-macrophage progenitors are present in adult bone marrow. Nat. Immunol. 2, 83–88 (2001).

    Article  CAS  Google Scholar 

  27. Ardavin, C.F. & Zapata, A. Ultrastructure and changes during metamorphosis of the lympho-hemopoietic tissue of the larval anadromous sea lamprey Petromyzon marinus. Dev. Comp. Immunol. 11, 79–93 (1987).

    Article  CAS  Google Scholar 

  28. Shintani, S. et al. Do lampreys have lymphocytes? The Spi evidence. Proc. Natl. Acad. Sci. USA 97, 7417–7422 (2000).

    Article  CAS  Google Scholar 

  29. Ardavin, C.F. & Zapata, A. The pharyngeal lymphoid tissue of lampreys. A morpho-functional equivalent of the vertebrate thymus? Thymus 11, 59–65 (1988).

    CAS  PubMed  Google Scholar 

  30. Pancer, Z., Mayer, W.E., Klein, J. & Cooper, M.D. Prototypic T cell receptor and CD4-like coreceptor are expressed by lymphocytes in the agnathan sea lamprey. Proc. Natl. Acad. Sci. USA 101, 13273–13278 (2004).

    Article  CAS  Google Scholar 

  31. Sakano, H., Huppi, K., Heinrich, G. & Tonegawa, S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature 280, 288–294 (1979).

    Article  CAS  Google Scholar 

  32. Agrawal, A., Eastman, Q.M. & Schatz, D.G. Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature 394, 744–751 (1998).

    Article  CAS  Google Scholar 

  33. Hiom, K., Melek, M. & Gellert, M. DNA transposition by the RAG1 and RAG2 proteins: a possible source of oncogenic translocations. Cell 94, 463–470 (1998).

    Article  CAS  Google Scholar 

  34. Kapitonov, V.V. & Jurka, J. RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons. PLoS Biol 3, e181 (2005).

    Article  Google Scholar 

  35. Eason, D.D. et al. Mechanisms of antigen receptor evolution. Semin. Immunol. 16, 215–226 (2004).

    Article  CAS  Google Scholar 

  36. Boehm, T. Co-evolution of a primordial peptide-presentation system and cellular immunity. Nat. Rev. Immunol. 6, 79–84 (2006).

    Article  CAS  Google Scholar 

  37. Dishaw, L.J., Smith, S.L. & Bigger, C.H. Characterization of a C3-like cDNA in a coral: phylogenetic implications. Immunogenetics 57, 1–14 (2005).

    Article  Google Scholar 

  38. Litman, G.W., Cannon, J.P. & Dishaw, L.J. Reconstructing immune phylogeny: new perspectives. Nat. Rev. Immunol. 5, 866–879 (2005).

    Article  CAS  Google Scholar 

  39. Nemazee, D. Receptor editing in lymphocyte development and central tolerance. Nat. Rev. Immunol. 6, 728–740 (2006).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  41. Ivanov, I.I. & Diehl, G.E. & Littman, D.R. Lymphoid tissue inducer cells in intestinal immunity. Curr. Top. Microbiol. Immunol. 308, 59–82 (2006).

    CAS  PubMed  Google Scholar 

  42. Drayton, D.L., Liao, S., Mounzer, R.H. & Ruddle, N.H. Lymphoid organ development: from ontogeny to neogenesis. Nat. Immunol. 7, 344–353 (2006).

    Article  CAS  Google Scholar 

  43. Austen, K.F. & Fearon, D.T. A molecular basis of activation of the alternative pathway of human complement. Adv. Exp. Med. Biol. 120B, 3–17 (1979).

    CAS  PubMed  Google Scholar 

  44. Matsunaga, T. & Rahman, A. What brought the adaptive immune system to vertebrates?–The jaw hypothesis and the seahorse. Immunol. Rev. 166, 177–186 (1998).

    Article  CAS  Google Scholar 

  45. Kyewski, B. & Derbinski, J. Self-representation in the thymus: an extended view. Nat. Rev. Immunol. 4, 688–698 (2004).

    Article  CAS  Google Scholar 

  46. Cordier, A.C. & Haumont, S.M. Development of thymus, parathyroids, and ultimo-branchial bodies in NMRI and nude mice. Am. J. Anat. 157, 227–263 (1980).

    Article  CAS  Google Scholar 

  47. Rossi, S.W., Jenkinson, W.E., Anderson, G. & Jenkinson, E.J. Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium. Nature 441, 988–991 (2006).

    Article  CAS  Google Scholar 

  48. Bleul, C.C. et al. Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature 441, 992–996 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Supported by the Max-Planck Society.

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  1. Max Planck Institute of Immunobiology, Freiburg, D-79279, Germany

    Thomas Boehm & Conrad C Bleul

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Boehm, T., Bleul, C. The evolutionary history of lymphoid organs. Nat Immunol 8, 131–135 (2007). https://doi.org/10.1038/ni1435

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