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Antibody responses of variable lymphocyte receptors in the lamprey

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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Figure 1: Production of VLRB antibodies after immunization with heterologous erythrocytes.
Figure 2: VLRB antibody composition.
Figure 3: VLRB antibody response to immunization with B. anthracis.
Figure 4: Tissue distribution of VLRB+ lymphocytes.
Figure 5: Antigen-binding VLRB+ cells before and after immunization with B. anthracis.
Figure 6: Proliferation of VLRB+ cells in lampreys immunized with B. anthracis exosporium.
Figure 7: Characterization of VLRB-secreting cells induced by immunization with B. anthracis exosporium.

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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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Correspondence to Max D Cooper.

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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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