Skip to main content
SpringerLink
Log in

Evolutionary Factors in the Emergence of the Combinatorial Germline Antibody Repertoire

  • Chapter
Phylogenetic Perspectives on the Vertebrate Immune System

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 484))

Abstract

Although life began on earth approximately 3.5 billion years ago, the combinatorial immune response apparently arose in a “big bang” approximately 450 million years ago, [1–4] coincident with the emergence of jawed vertebrates. Preceding this event was the so-called Cambrian explosion occurring approximately 545 million years ago that resulted in the seemingly rapid appearance of virtually all living forms as represented by the fossil record [5, 6]. However, molecular investigations seeking to calibrate evolutionary clocks and analyze phylogenetic relationships indicate that the explosive phases of evolution implied by the fossil record may have been preceded by extended periods of inconspicuous innovation [5, 6] in possible living organisms thatdid not become part of the currently available fossil record. The necessary elements of the combinatorial immune system, immunoglobulins (Igs), T-cell receptors (TCR), MHC products and recombinase activator genes (RAG) are clearly present in even the most primitive jawed vertebrates, the chondrichthian fishes [7–10] which appeared in evolution approximately 450 million years ago. Definitive evidence for these elements is thus far lacking in agnathan vertebrates and in lower deuterostomes. Nevertheless, many primordial elements upon which the combinatorial system is built may well have preceded the split in evolution between protostomes and deuterostomes and their origins may even extrapolate back to ancient times corresponding to the origin and evolution of bacteria.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Marchalonis, J.J., and S.F. Schluter. 1990. On the relevance of invertebrate recognition and defense mechanisms to the emergence of the immune response of vertebrates.Scand. J. Immunol.32:13.

    Article  PubMed  CAS  Google Scholar 

  2. Marchalonis, J.J., and S.F. Schluter. 1998. A stochastic model for the rapid emergence of specific vertebrate immunity incorporating horizontal transfer of systems enabling duplication and combinatorial diversification.J. Theo. Biol.193:429.

    Article  CAS  Google Scholar 

  3. Schluter, S.F., R.M. Bernstein, H. Bernstein, and J.J. Marchalonis. 1999. `Big Bang’ emergence of the combinatorial immune system. Dev & Comp. Immunol. 23:107.

    Article  CAS  Google Scholar 

  4. Thompson, C.B. 1995. New Insights into V(D)J recombination and its role in the evolution of the immune system.Immunity3:531.

    Article  PubMed  CAS  Google Scholar 

  5. Cooper, A., and R. Fortey. 1998. Evolutionary explosions and the phylogenetic fuse.Tree13:151.

    PubMed  CAS  Google Scholar 

  6. Wray, G.A., J.S. Levinton, and L.H. Shapiro. 1996. Molecular evidence for deep precambrian divergencies among metazoan phyla.Science274:568.

    Article  CAS  Google Scholar 

  7. Marchalonis, J.J., S.F. Schluter, R.M. Bernstein, and A.B. Edmundson. 1998. Phylogenetic emergence and molecular evolution of the immunoglobulin family.Adv. in Immunol.70:417.

    Article  CAS  Google Scholar 

  8. Marchalonis, J.J., S.F. Schluter, R.M. Bernstein, and V.S. Hohman. 1998. Antibodies of Sharks: revolution and evolution.Immunol. Rev.166:103.

    Article  PubMed  CAS  Google Scholar 

  9. Litman, G.W., M.K. Anderson, and J.P. Rast. 1999. Evolution of antigen binding receptors.Annu. Rev. Immunol.17:109.

    Article  PubMed  CAS  Google Scholar 

  10. Du Pasquier, L., and M. Flajnik. 1999. Origin and evolution of the vertebrate immune system. In Fundamental Immunoloty, vol. 4th Edition. Raven Press, New York. 199.

    Google Scholar 

  11. Doolittle, W.F. 1999. Phylogenetic Classification and the Universal tree.Science284:2124.

    Article  PubMed  CAS  Google Scholar 

  12. Agrawal, A., Q.M. Eastman, and D.G. Schatz. 1998. Transposition mediated by RAGI and RAG2 and its implications for the evolution of the immune system.Nature394:744.

    Article  PubMed  CAS  Google Scholar 

  13. Hiom, K., M. Melek, and M. Gellert. 1998. DNA transposition by the RAGI and RAG2 proteins: a possible source of oncogenic translocations.Cell94:463.

    Article  PubMed  CAS  Google Scholar 

  14. Williams, A.F., and A.N. Barclay. 1988. The immunoglobulin superfamily - domains for cell surface recognition.Ann.Rev. Immunol.6:381.

    Article  CAS  Google Scholar 

  15. Bork, P., L. Holm, and C. Sander. 1994. The Immunoglobulin Fold. Structural classification, sequence patterns and common core.J. Mol. Biol.242:309.

    PubMed  CAS  Google Scholar 

  16. Doolittle, R.F. 1995. The multiplicity of domains in proteins.Annu. Rev. Biochem.64:287.

    Article  PubMed  CAS  Google Scholar 

  17. Holmgren, A., M.J. Kuehn, C.-I. Branden, and S.J. Hultgren. 1992. Conserved immunoglobulin-like features in a family of periplasmic pilus chaperones in bacteria. EMBO J.:1617.

    Google Scholar 

  18. Klein, J. 1997. Homology between immune responses in vertebrates and invertebrates: does it exist? Scand. J. Immunol46:558.

    Article  PubMed  CAS  Google Scholar 

  19. Hughes, A.L. 1998. Protein phylogenics provide evidence of a radical discontinuity between arthropod and vertebrate immune systems.Immunogenet47:283.

    Article  CAS  Google Scholar 

  20. Klein, J. 1989. Are invertebrates capable of anticipatory immune responses?Scand. J. Immunol.29:499.

    Article  PubMed  CAS  Google Scholar 

  21. Lambris, J.D., K.B.M. Reid, and J.E. Volanakis. 1999. The Evolution, structure, biology and pathophysiology of complement.Immunol. Today20:207.

    Article  PubMed  CAS  Google Scholar 

  22. Smith, L.C., C.-S. Shill, and S.G. Dachenhausen. 1998. Coelomocytes express SpBf, a homologue of factor B, the second component in the sea urchin complement system../.Immunol.161:6784.

    CAS  Google Scholar 

  23. Armstrong, P.B., W.F. Mangel, J.S. Wall, J.F. Hainfield, K.E. Van Holde, A. Ikai, and J.P. Quigley. 1991. Structure of a2-macroglobulin from the arthropodLimulus polyphemus. J. Biol. Chem.266:2526.

    CAS  Google Scholar 

  24. Hoffman, J.A., F.C. Kafatos, C.A.J. Janeway, and R.A.B. Ezekowitz. 1999. Phylogenetic perspectives in innate immunity.Science284:1313.

    Article  Google Scholar 

  25. Fearon, D.T., and R.M. Locksley. 1996. The instructive role of innate immunity in the acquired immune response.Science272:50.

    Article  PubMed  CAS  Google Scholar 

  26. Medzhitov, R., and C.A. Janeway. 1997. Innate Immunity: The virtues of a nonclonal system of recognition.Cell91:295.

    Article  PubMed  CAS  Google Scholar 

  27. Lieber, C.S. 1997. Cytochrome P-4502E1: Its physiological and pathological role.Physiol. Revs77:517.

    CAS  Google Scholar 

  28. Payne, C.M., C. Crowley, D. Washo-Stutltz, M. Briehl, H. Bernstein, C. Bernstein, S. Beard, H. Holubec, and J. Wameke. 1998. The stress-response protein poly(ADP-ribose) polymerase and NKkB oritect against bile salt-induced apoptosis.Cell Death & Different.5:623.

    Article  CAS  Google Scholar 

  29. Zapata, A., C.F. Ardavin, R.P. Gomariz, and J. Leceta. 1981. Plasma cells of the amniocoete ofPetromyzon marinus. Cell liiss. Res.221:203.

    Article  CAS  Google Scholar 

  30. Marchalonis, J.J., and G.M. Edelman. 1968. Phylogenetic origins of antibody structure. III. Immunoglobulins from the sea lampreyPetromyzon marinas. J. Exp. Med.127:891.

    Article  CAS  Google Scholar 

  31. Raison, R.L., and W.H. Hildemann. 1984. Immunoglobulin-bearing blood leucocytes in the Pacific hagfish.Dev. Comp. Immunol.8:99.

    Article  PubMed  CAS  Google Scholar 

  32. Vamer, J., P. Neame, and G.W. Litman. 1991. A serum heterodimer from hagfish(Eptatretus stoutii)exhibits structural similarity and partial sequence homology with immunoglobulin.Proc. Natl. Acad. Sci. USA88:1746.

    Article  Google Scholar 

  33. Kay, M.M.B., C. Cover, S.F. Schluter, R.M. Bernstein, and J.J. Marchalonis. 1995. Band 3, the anion transporter, is conserved during evolution: implications fro aging and vertebrate evolution.Cell. & Mol. Biol.41:833.

    CAS  Google Scholar 

  34. Najakshin, A.M., L.V. Mechetina, B.Y. Alabyev, and A.V. Taranin. 1999. Identification of an IL-8 homolog in lamprey(Lampetra fluviatiles):early evolutionary divergence of chemokines.Eur. J. Immunol.29:375.

    Article  PubMed  CAS  Google Scholar 

  35. Goodier, J.L., and W.S. Davidson. 1994. Tcl Transposon-like sequences are widely distributed in Salmonids.JMol Biol241:26.

    Article  CAS  Google Scholar 

  36. Ivies, Z., P.B. Hackett, R.H. Plasterk, and Z. Izsvak. 1997. Molecular reconstruction ofSleeping BeautyaTcl-liketransposon from fish, and its transposition in human cells.Cell91:501.

    Article  Google Scholar 

  37. Britten, R.J. 1997. Mobile elements inserted in the distant past have taken on important functions.Gene205:177.38.

    Google Scholar 

  38. Gaudieri, S., C. Leelayuwat, D.C. Townend, J.K. Kulski, and R.L. Dawkins. 1997. Genomic characterization of the region between HLA-B and TNF: implications for the evolution of multicopy gene families.J. Mol. Evol.44:5147.

    Article  Google Scholar 

  39. Ghaffari, S.H., and C.J. Lobb. 1999. Structure and genomic organization of a second cluster of immunoglobulin heavy chain gene segments in the channel catfish.J. Immunol.162:1519.

    PubMed  CAS  Google Scholar 

  40. Marchalonis, J.J., G.R. Vasta, G.W. Warr, and W.C. Barker. 1984. Probing the boundaries of the extended immunoglobulin family of recognition moelcules: Jumping domains, convergences and minigenes.Immunol. Today5:133.

    Article  CAS  Google Scholar 

  41. Andersson, E., and T. Matsunaga. 1993. Complete cDNA sequence of a rainbow trout IgM gene and evolution of vertebrate IgM constant domains.Immunogenet38:243.

    Article  CAS  Google Scholar 

  42. Kimura, M. 1969. The rate of molecular evolution considered from the standpoint of population genetics.Proc. Natl. Acad. Sci. USA63:1181.

    Article  PubMed  CAS  Google Scholar 

  43. Ayala, F.J. 1997. Vagaries of the molecular clock.Proc Natl Acad Sci USA94:7776.

    Article  PubMed  CAS  Google Scholar 

  44. Klein, J. 1998. In an immunological twilight zone.Proc. Natl. Acad. Sci. USA95:11504.

    Article  PubMed  CAS  Google Scholar 

  45. Papermaster, B.W. 1966. Genetic considerations of immunoglobulin evolution in vertebrates.InPhylogeny of Immunity. R.T. Smith, P.A. Miescher and R.A. Good, editors. University of Florida Press, Gainesville, FL. 118.

    Google Scholar 

  46. Makela, O., and G.W. Litman. 1980. Lack of heterogeneity in anti-hapten antibodies of a phylogenetically primitive shark.Nature287:639.

    Article  PubMed  CAS  Google Scholar 

  47. Clem, L.W., W.E. McLearn, and V. Shankey. 1975. Quantitative and habitative aspects of the antibody library of sharks.Adv. Exp. Med. Biol.64:231.

    PubMed  CAS  Google Scholar 

  48. Hinds-Frey, K.R., H. Nishikata, R.T. Litman, and G.W. Litman. 1993. Somatic variation precedes extensive diversification of germline sequences combinatorial joining in the evolution of immunoglobulin heavy chain diversity.J Exp Med178:815.

    Article  PubMed  CAS  Google Scholar 

  49. Diaz, M., J. Velez, M. Singh, J. Cerny, and M.F. Flajnik. 1999. Mutational pattern of the nurse shark antigen receptor gene (NAR) is similar to that of mammalian Ig genes and to spontaneous mutations in evolution: the translesion synthesis model of somatic hypermutation.Intl. Immunol.11:825.

    Article  CAS  Google Scholar 

  50. Hinds, K.R., and G.W. Litman. 1986. Major reorganization of immunoglobulin VH segmental elements during vertebrate evolution.Nature (Ldn)320:546.

    Article  CAS  Google Scholar 

  51. Hohman, V.S., D.B. Schuchman, S.F. Schluter, and J.J. Marchalonis. 1993. Genomie clone for sandbar shark I light chain: generation of diversity in the absence of gene rearrangement.Proc Natl Acad Sci USA90:9882.

    Article  PubMed  CAS  Google Scholar 

  52. Rast, J.P., M.K. Anderson, T. Ota, R.T. Litman, M. Margittal, M.J. Shamblott, and G.W. Litman. 1994. Immunoglobulin light chain class multiplicity and alternative organizational forms in early vertebrate phylogeny.Immunogenet.40:83.

    Article  CAS  Google Scholar 

  53. Harindranath, N., H. Ikematsu, A.L. Notkins, and P. Casali. 1993. Structure of the V. and VLsegments of polyreactive and monoreactive human natural antibodies to HIV-1 andescherchia colibgalactosidase.Int Immunol5:1523.

    Article  PubMed  CAS  Google Scholar 

  54. Coutinho, A., M.D. Kazatchkine, and S. Avrameas. 1995. Natural autoantibodies.Curr. Opin. in Immunol7:812.

    Article  CAS  Google Scholar 

  55. Gonzalez, R., J. Charlemagne, W. Mahana, and S. Avrameas. 1988. Specificity of natural serum antibodies present in phylogenetically distinct fish species.Immunology63:31.

    PubMed  CAS  Google Scholar 

  56. Marchalonis, J.J., V.S. Hohman, C. Thomas, and S.F. Schluter. 1993. Antibody production in sharks and humans: a role for natural antibodies.Dev Comp Immunol17:41.

    Article  PubMed  CAS  Google Scholar 

  57. Rudikoff, S., E.W. Voss, and S. M.M. 1970. Biological and Chemical properties of natural antibodies in the nurse shark.J. Immunol.105, no. 6:1344.

    PubMed  CAS  Google Scholar 

  58. Leslie, G.A., and L.W. Clem. 1970. Reactivity of normal shark immunoglobulin with nitrophenyl ligands.J. Immunol.105:1547.

    PubMed  CAS  Google Scholar 

  59. Landsteiner, K. 1962. The specificity of Serological Reactions. Dover Publications, Inc., New York.

    Google Scholar 

  60. Marchalonis, J.J., A. Garza, W.J. Landsperger, S.F. Schluter, and A.-C. Wang. 1997. Binding of human IgG myeloma proteins to autologous T-cell receptor determinants.Crit. Rev. in Immunol.17:497.

    CAS  Google Scholar 

  61. Marchalonis, J.J., I. Robey, S.F. Schluter, and D.E. Yocum. 1999. Epitope promiscuity of human monoclonal autoantibodies to T-cell receptor combining site determinants.App. Biochem. & Biotech.submitted.

    Google Scholar 

  62. Kramer, A., T. Keitcl, K. Winkler, W. Stocklein, W. Hohne, and J. Schneider-Mergener. 1997. Molecular basis for the binding promiscuity of an anti-p24 (HIV-1) monoclonal antibody.Cell91:799.

    Article  PubMed  CAS  Google Scholar 

  63. Keitel, T., A. Kramer, H. Wessner, C. Scholz, J. Schneider-Mergener, and W. Hohne. 1997. Crystallographic analysis of Anti-p24 (HIV-1) monoclonal antibody cross-reactivity and polyspecificity.Cell91:811.

    Article  PubMed  CAS  Google Scholar 

  64. Velick, S.F., C.W. Parker, and H.N. Eisen. 1960. Excitation energy transfer and the quantitative study of the antibody hapten reaction.Proc. Natl. Acad. Sci. USA46:1470.

    Article  PubMed  CAS  Google Scholar 

  65. Arkoosh, M.R., and S.L. Kaattari. 1991. Development of immunological memory in rainbow trout(Oncorhynhus mykiss) Ian immunochemical and cellular analysis of the B cell response.Dey. & Comp. Immunol.15:279.

    Article  CAS  Google Scholar 

  66. Kay, M.M.B. 1984. Localization of senescent cell antigen on band 3.Proc. Natl. Acad. Sci. USA81:5753.

    Article  PubMed  CAS  Google Scholar 

  67. Carson, D.A., P.P. Chen, R.I. Fox, T.J. Kipps, F. Jirik, R.D. Goldfien, G. Silverman, V. Radoux, and S. Fong. 1987. Rheumatoid factor and immune networks.Annu. Rev. Immunol5:109.

    Article  PubMed  CAS  Google Scholar 

  68. Yan, X., S.V. Evans, M.J. Kaminki, S.D. Gillies, R.A. Reisfeld, A.N. Houghton, and P.B. Chapman. 1996. Characterization of an Ig VH idiotope that results in specific homophilic binding and increased avidity for antigen.J. Immunol.157:1582.

    PubMed  CAS  Google Scholar 

  69. Bcrgenbrant, S., A. Osterborg, G. Holm, H. Mellstedt, and A.K. Lefvert. 1991. Anti-idiotypic antibodies in patients with monoclonal gammopathies: relation to the tumour load.Brit. J. Haematology78:66.

    Article  Google Scholar 

  70. Marchalonis, J.J., S.F. Schluter, E. Wang, K. Dehghanpisheh, D. Lake, D.E. Yocum, A.B. Edmundson, and J.B. Winfield. 1994. Synthetic autoantigens of immunoglobulins and T-cell receptors: their recognition in aging, infection and autoimmunity.Proc. Soc. Expt. Biol.207:129.

    CAS  Google Scholar 

  71. Dehghanpisheh, K., and J.J. Marchalonis. 1997. Retrovirally induced mouse anti-TCR monoclonals can synergize thein vitroproliferative T cell response to bacterial superantigens.Scand. J. Immunol.45:645.

    Article  PubMed  CAS  Google Scholar 

  72. Harnett, W., and M.M. Harnett. 1999. Phosphorylcholine: friend or foc of the immune system?Immunol. Today28:125.

    Article  Google Scholar 

  73. Volanakis, J.E., Y. Xu, and K.J. Macon. 1990. Human C-reactive protein and host defense.InDefense Molecules. J.J.M.a.C.L. Reinisch, editor. Wiley-Liss, Inc., New York. 161.

    Google Scholar 

  74. Vasta, G.R., J.J. Marchalonis, and H. Kohler. 1984. Invertebrate recognition protein cross-reacts with an immunoglobulin idiotype.J Exp Med159:1270.

    Article  PubMed  CAS  Google Scholar 

  75. Briles, D.E., J.L. Claflin, K. Schroer, and C. Formann. 1981. Mouse Igg3 antibodies are highly protective against infection with Streptococcus pneumoniae.Nature294:88.

    Article  PubMed  CAS  Google Scholar 

  76. Shen, S.Y., R.M. Bernstein, S.F. Schluter, and J.J. Marchalonis. 1996. Heavy chain variable regions in carcharhine sharks: development of a comprehensive model for the evolution of VH domains among the gnathanstomes.Immunol. & Cell. Biol.74:357.

    Article  CAS  Google Scholar 

  77. Rast, J.P., C.T. Anmemiya, R.T. Litman, S.J. Strong, and G.W. Litman. 1998. Distinct patterns of IgH structure and organization in a divergent lineage of chondrichthyan fishes.Immunogenet.47:234.

    Article  CAS  Google Scholar 

  78. Greenberg, A.S., L. Steiner, M. Kasahara, and M.F. Flajnik. 1993. Isolation of a shark immunoglobulin light chain CDNA clone encoding a protein resembling mammalian k light chains: implications for the evolution of light chains.Immunology90:10603.

    CAS  Google Scholar 

  79. Greenberg, A.S., D. Avila, M. Hughes, A. Hughes, E.C. McKinney, and Flajnik. 1995. A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks.Nature374:168.

    Article  PubMed  CAS  Google Scholar 

  80. Robey, F.A., T. Tanaka, and T.Y. Liu. 1983. Isolation and characterization of two major serum proteins from the dogfishMustelus canisC-reactive protein and amyloid P component. J. Biol. Chem. 258:3889.

    PubMed  CAS  Google Scholar 

  81. Hawke, N.S., J.P. Rast, and G.W. Litman. 1996. Extensive diversity of transcribed TCR-beta in a phylogenetically primitive vertebrate.J Immunol156:2458.

    PubMed  CAS  Google Scholar 

  82. Lake, D.F., S.F. Schluter, E. Wang, R.M. Bernstein, A.B. Edmundson, and J.J. Marchalonis. 1994. Autoantibodies to the ab T-cell receptors in human immunodeficiency virus (HIV) infection: dysregulation and mimcry.Proc. Natl. Acad Sci. USA91:10849.

    Article  PubMed  CAS  Google Scholar 

  83. Sledge, C., L.W. Clem, and L.E. Hood. I974. Antibody structure: amino terminal sequence of nurse shark light and heavy chains.J. Immunol.112:941.

    Google Scholar 

  84. Clarke, S.H., J.L. Chaffin, M. Potter, and S. Rudikoff. 1983. Polymorphisminanti-phosphorylcholine antibodies reflecting evolution of immunoglobulin families.J. Exp. Med.157:98.

    Article  PubMed  CAS  Google Scholar 

  85. Hohman, V.S., S.F. Schluter, and J.J. Marchalonis. 1992. Complete sequence of a CDNA clone specifying sandbar shark immunoglobulin light chain: gene organization and implications for the evolution of light chains.Proc Natl Acad Sci USA89:276.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Microbiology and Immunology College of Medicine, University of Arizona, Tucson, AZ, 85724

    John J. Marchalonis, Miranda K. Adelman, Brian J. Zeitler, Paul M. Sarazin, P. Michael Jaqua & Samuel F. Schluter

Authors
  1. John J. Marchalonis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Miranda K. Adelman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian J. Zeitler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul M. Sarazin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Michael Jaqua
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Samuel F. Schluter
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Massachusetts Boston, Boston, Massachusetts, USA

    Gregory Beck  & Manickam Sugumaran  & 

  2. University of California, Los Angeles, Los Angeles, California, USA

    Edwin L. Cooper

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Science+Business Media New York

About this chapter

Cite this chapter

Marchalonis, J.J., Adelman, M.K., Zeitler, B.J., Sarazin, P.M., Jaqua, P.M., Schluter, S.F. (2001). Evolutionary Factors in the Emergence of the Combinatorial Germline Antibody Repertoire. In: Beck, G., Sugumaran, M., Cooper, E.L. (eds) Phylogenetic Perspectives on the Vertebrate Immune System. Advances in Experimental Medicine and Biology, vol 484. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1291-2_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1291-2_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5481-9

  • Online ISBN: 978-1-4615-1291-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation