Abstract
Lamprey and hagfish, the living representatives of jawless vertebrates, use genomic leucine-rich-repeat cassettes for the combinatorial assembly of diverse antigen receptor genes encoding variable lymphocyte receptors of two types: VLRA and VLRB. We describe here the VLRB-bearing lineage of lymphocytes in sea lamprey. These cells responded to repetitive carbohydrate or protein determinants on bacteria or mammalian cells with lymphoblastoid transformation, proliferation and differentiation into plasmacytes that secreted multimeric antigen-specific VLRB antibodies. Lacking a thymus and the ability to respond to soluble protein antigens, lampreys seem to have evolved a B cell–like system for adaptive humoral responses.
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References
Pancer, Z. et al. Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey. Nature 430, 174–180 (2004).
Alder, M.N. et al. Diversity and function of adaptive immune receptors in a jawless vertebrate. Science 310, 1970–1973 (2005).
Pancer, Z. et al. Variable lymphocyte receptors in hagfish. Proc. Natl. Acad. Sci. USA 102, 9224–9229 (2005).
Kim, H.M. et al. Structural diversity of the hagfish variable lymphocyte receptors. J. Biol. Chem. 282, 6726–6732 (2007).
Rogozin, I.B. et al. Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase. Nat. Immunol. 8, 647–656 (2007).
Nagawa, F. et al. Antigen-receptor genes of the agnathan lamprey are assembled by a process involving copy choice. Nat. Immunol. 8, 206–213 (2007).
Finstad, J. & Good, R.A. The evolution of the immune response. 3. Immunologic responses in the lamprey. J. Exp. Med. 120, 1151–1168 (1964).
Boffa, G.A., Fine, J.M., Drilhon, A. & Amouch, P. Immunoglobulins and transferrin in marine lamprey sera. Nature 214, 700–702 (1967).
Marchalonis, J.J. & Edelman, G.M. Phylogenetic origins of antibody structure. 3. Antibodies in the primary immune response of the sea lamprey, Petromyzon marinus. J. Exp. Med. 127, 891–914 (1968).
Linthicum, D.S. & Hildemann, W.H. Immunologic responses of Pacific hagfish. 3. Serum antibodies to cellular antigens. J. Immunol. 105, 912–918 (1970).
Pollara, B., Litman, G.W., Finstad, J., Howell, J. & Good, R.A. The evolution of the immune response. VII. Antibody to human “O” cells and properties of the immunoglobulin in lamprey. J. Immunol. 105, 738–745 (1970).
Litman, G.W., Finstad, F.J., Howell, J., Pollara, B.W. & God, R.A. The evolution of the immune response. 3. Structural studies of the lamprey immuoglobulin. J. Immunol. 105, 1278–1285 (1970).
Fujii, T., Nakagawa, H. & Murakawa, S. Immunity in lamprey. I. Production of haemolytic and haemagglutinating antibody to sheep red blood cells in Japanese lampreys. Dev. Comp. Immunol. 3, 441–451 (1979).
Hagen, M., Filosa, M.F. & Youson, J.H. The immune response in adult sea lamprey (Petromyzon marinus L.): the effect of temperature. Comp. Biochem. Physiol. A 82, 207–210 (1985).
Steichen, C., Chen, P., Kearney, J.F. & Turnbough, C.L., Jr. Identification of the immunodominant protein and other proteins of the Bacillus anthracis exosporium. J. Bacteriol. 185, 1903–1910 (2003).
Acton, R.T., Weinheimer, P.F., Hildemann, W.H. & Evans, E.E. Induced bactericidal response in the hagfish. J. Bacteriol. 99, 626–628 (1969).
Acton, R.T., Weinheimer, P.F., Hildemann, W.H. & Evans, E.E. Bactericidal antibody response in the Pacific hagfish, Eptatretus stoutii. Infect. Immun. 4, 160–166 (1971).
Purvis, H.A. in Technical Report No. 35 1–36 (Great Lakes Fishery Commission, Ann Arbor, 1979).
Prieto, P.A. et al. Expression of human H-type α1,2-fucosyltransferase encoding for blood group H(O) antigen in Chinese hamster ovary cells. Evidence for preferential fucosylation and truncation of polylactosamine sequences. J. Biol. Chem. 272, 2089–2097 (1997).
Boydston, J.A., Chen, P., Steichen, C.T. & Turnbough, C.L.,, Jr. Orientation within the exosporium and structural stability of the collagen-like glycoprotein BclA of Bacillus anthracis. J. Bacteriol. 187, 5310–5317 (2005).
Potter, I.C., Percy, R., Barber, D.L. & Macey, D.J. in The Morphology, Development and Physiology of Blood Cells (eds. Hardisty, M.W. & Potter, I.C.) Ch. 32, 233–286 (Academic, London, 1982).
Finstad, J., Papermaster, B.W. & Good, R.A. Evolution of the immune response. II. Morphologic studies on the origin of the thymus and organized lymphoid tissue. Lab. Invest. 13, 490–512 (1964).
Boehm, T. & Bleul, C.C. The evolutionary history of lymphoid organs. Nat. Immunol. 8, 131–135 (2007).
Kasamatsu, J., Suzuki, T., Ishijima, J., Matsuda, Y. & Kasahara, M. Two variable lymphocyte receptor genes of the inshore hagfish are located far apart on the same chromosome. Immunogenetics 59, 329–331 (2007).
Kroczek, R.A., Gunter, K.C., Germain, R.N. & Shevach, E.M. Thy-1 functions as a signal transduction molecule in T lymphocytes and transfected B lymphocytes. Nature 322, 181–184 (1986).
Hundt, M. & Schmidt, R.E. The glycosylphosphatidylinositol-linked Fcγ receptor III represents the dominant receptor structure for immune complex activation of neutrophils. Eur. J. Immunol. 22, 811–816 (1992).
Stefanova, I. et al. Lipopolysaccharide induces activation of CD14-associated protein tyrosine kinase p53/56lyn. J. Biol. Chem. 268, 20725–20728 (1993).
Ishii, A. et al. Lamprey TLRs with properties distinct from those of the variable lymphocyte receptors. J. Immunol. 178, 397–406 (2007).
Pancer, Z. & Cooper, M.D. The evolution of adaptive immunity. Annu. Rev. Immunol. 24, 497–518 (2006).
Cooper, M.D. & Alder, M.N. The evolution of adaptive immune systems. Cell 124, 815–822 (2006).
Forey, P.L. & Janvier, P. Agnathans and the origin of jawed vertebrates. Nature 361, 129–134 (1993).
Fujii, T., Nakagawa, H. & Murakawa, S. Immunity in lamprey. II. Antigen-binding responses to sheep erythrocytes and hapten in the ammocoete. Dev. Comp. Immunol. 3, 609–620 (1979).
Kilarski, W. & Plytycz, B. The presence of plasma cells in the lamprey (Agnatha). Dev. Comp. Immunol. 5, 361–366 (1981).
Zapata, A., Ardavin, C.F., Gomariz, R.P. & Leceta, J. Plasma cells in the ammocoete of Petromyzon marinus. Cell Tissue Res. 221, 203–208 (1981).
Fujii, T. Electron microscopy of the leucocytes of the typhlosole in ammocoetes, with special attention to the antibody-producing cells. J. Morphol. 173, 87–100 (1982).
Hagen, M., Filosa, M.F. & Youson, J.H. Immunocytochemical localization of antibody-producing cells in adult lamprey. Immunol. Lett. 6, 87–92 (1983).
Herrin, B.R. et al. Structure and specificity of lamprey monoclonal antibodies. Proc. Natl. Acad. Sci. USA, published online 18 January 2008 (doi:10.1073/pnas.0711619105).
Rusu, V.M. & Cooper, M.D. In vivo effects of cortisone on the B cell line in chickens. J. Immunol. 115, 1370–1374 (1975).
Igarashi, H. et al. Early lymphoid progenitors in mouse and man are highly sensitive to glucocorticoids. Int. Immunol. 17, 501–511 (2005).
Ashwell, J.D., Lu, F.W. & Vacchio, M.S. Glucocorticoids in T cell development and function. Annu. Rev. Immunol. 18, 309–345 (2000).
Bryan, M.B. et al. Patterns of invasion and colonization of the sea lamprey (Petromyzon marinus) in North America as revealed by microsatellite genotypes. Mol. Ecol. 14, 3757–3773 (2005).
Kearney, J.F., Radbruch, A., Liesegang, B. & Rajewsky, K. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J. Immunol. 123, 1548–1550 (1979).
Shi, S.R., Cote, R.J. & Taylor, C.R. Antigen retrieval immunohistochemistry: past, present, and future. J. Histochem. Cytochem. 45, 327–343 (1997).
Oliva, C. et al. The integrin Mac-1 (CR3) mediates internalization and directs Bacillus anthracis spores into professional phagocytes. Proc. Natl. Acad. Sci. USA 105, 1261–1266 (2008).
Acknowledgements
We thank L. Stansell for providing human erythrocytes; L. Millican and E. Weeks for assistance with electron microscopy; and M. Flurry for help with the preparation of figures. Supported by the National Institutes of Health (AI72435 and AI57699).
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M.N.A., B.R.H., W.E.G., C.L.T. and M.D.C. designed the research; M.N.A., B.R.H. and A.S. did the research; C.R.S., L.A.G., G.L.G. and J.A.B. contributed new reagents and/or analytic tools; M.N.A., B.R.H., A.S., G.L.G., W.E.G., C.L.T. and M.D.C. analyzed data; and M.N.A. and M.D.C. wrote the paper.
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Alder, M., Herrin, B., Sadlonova, A. et al. Antibody responses of variable lymphocyte receptors in the lamprey. Nat Immunol 9, 319–327 (2008). https://doi.org/10.1038/ni1562
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DOI: https://doi.org/10.1038/ni1562
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