A thymus candidate in lampreys

Nature. 2011 Feb 3;470(7332):90-4. doi: 10.1038/nature09655.


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 allografts but were found to lack the immunoglobulin-based adaptive immune system of jawed vertebrates. 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), 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 genes. These clonally diverse anticipatory antigen receptors are assembled from incomplete genomic fragments by gene conversion, which is thought to be initiated by either of two genes encoding cytosine deaminase, cytosine deaminase 1 (CDA1) in T-like cells and CDA2 in B-like cells. 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 place. 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), a marker of the thymopoietic microenvironment in jawed vertebrates, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Cell Proliferation
  • Fish Proteins / genetics
  • Fish Proteins / metabolism
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation / immunology
  • Gills / anatomy & histology
  • Gills / immunology
  • Immunization
  • Lampreys / anatomy & histology*
  • Lampreys / genetics
  • Lampreys / immunology*
  • Larva / anatomy & histology
  • Larva / immunology
  • Larva / metabolism
  • Lymphocytes / cytology
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Mitogens / immunology
  • Organ Specificity
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Thymus Gland / anatomy & histology
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism


  • Fish Proteins
  • Forkhead Transcription Factors
  • Mitogens
  • Receptors, Immunologic
  • Whn protein