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Dual nature of the adaptive immune system in lampreys

Nature volume 459, pages 796–801 (2009)Cite this article

A Corrigendum to this article was published on 20 August 2009

Abstract

Jawless vertebrates use variable lymphocyte receptors (VLR) comprised of leucine-rich-repeat (LRR) segments as counterparts of the immunoglobulin-based receptors that jawed vertebrates use for antigen recognition. Highly diverse VLR genes are somatically assembled by the insertion of variable LRR sequences into incomplete germline VLRA and VLRB genes. Here we show that in sea lampreys (Petromyzon marinus) VLRA and VLRB anticipatory receptors are expressed by separate lymphocyte populations by monoallelic VLRA or VLRB assembly, together with expression of cytosine deaminase 1 (CDA1) or 2 (CDA2), respectively. Distinctive gene expression profiles for VLRA+ and VLRB+ lymphocytes resemble those of mammalian T and B cells. Although both the VLRA and the VLRB cells proliferate in response to antigenic stimulation, only the VLRB lymphocytes bind native antigens and differentiate into VLR antibody-secreting cells. Conversely, VLRA lymphocytes respond preferentially to a classical T-cell mitogen and upregulate the expression of the pro-inflammatory cytokine genes interleukin-17 (IL-17) and macrophage migration inhibitory factor (MIF). The finding of T-like and B-like lymphocytes in lampreys offers new insight into the evolution of adaptive immunity.

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Figure 1: VLRA and VLRB expression define distinct lymphocyte populations.
Figure 2: Monoallelic assembly of VLRA and VLRB genes.
Figure 3: Differential gene expression profiles of VLRA + and VLRB + lymphocytes.
Figure 4: Antigen-activated VLRA + lymphocytes do not secrete their receptors.
Figure 5: PHA preferentially stimulates VLRA + lymphocytes.

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Acknowledgements

We thank M. N. Alder and G. R. A. Ehrhardt for suggestions and discussion; C. L. Turnbough, Jr for providing B. anthracis spores and exosporium; D. E. Briles and W. H. Benjamin, Jr for E. coli, S. pneumoniae and S. typhimurium; H. Yi for help with electron microscopy; S. A. Durham and R. E. Karaffa, II for help with cell sorting; M. Flurry for help with preparation of figures. This work is supported by the National Institutes of Health and the Georgia Research Alliance.

Author Contributions P.G., M.H., B.R.H., J.L., C.Y., A.S. and M.D.C. designed the research, analysed data and wrote the paper; P.G., M.H., B.R.H., J.L., C.Y. and A.S. performed the research.

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  1. Peng Guo, Masayuki Hirano and Brantley R. Herrin: These authors contributed equally to this work.

Authors and Affiliations

  1. Emory Vaccine Center and Department of Pathology and Laboratory Medicine, Emory University, 1462 Clifton Road North-East, Atlanta, Georgia 30322, USA,

    Peng Guo, Masayuki Hirano, Brantley R. Herrin, Jianxu Li, Cuiling Yu, Andrea Sadlonova & Max D. Cooper

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Correspondence to Max D. Cooper.

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Guo, P., Hirano, M., Herrin, B. et al. Dual nature of the adaptive immune system in lampreys. Nature 459, 796–801 (2009). https://doi.org/10.1038/nature08068

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