Skip to main content
SpringerLink
Log in

The Natural Autoantibody Repertoire in Newborns and Adults

A Current Overview

  • Chapter
Naturally Occurring Antibodies (NAbs)

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 750))

Abstract

Antibody networks have been studied in the past based on the connectivity between idiotypes and anti-idiotypes—antibodies that bind one another. Here we call attention to a different network of antibodies, antibodies connected by their reactivities to sets of antigens—the antigen-reactivity network. The recent development of antigen microarray chip technology for detecting global patterns of antibody reactivities makes it possible to study the immune system quantitatively using network analysis tools. Here, we review the analyses of IgM and IgG autoantibody reactivities of sera of mothers and their offspring (umbilical cords) to 300 defined self-antigens; the autoantibody reactivities present in cord blood represent the natural autoimmune repertories with which healthy humans begin life and the mothers’ reactivities reflect the development of the repertoires in healthy young adults. Comparing the cord and maternal reactivities using several analytic tools led to the following conclusions: (1) The IgG repertoires showed a high correlation between each mother and her newborn; the IgM repertoires of all the cords were very similar and each cord differed from its mother’s IgM repertoire. Thus, different humans are born with very similar IgM autoantibodies produced in utero and with unique IgG autoantibodies found in their individual mothers. (2) Autoantibody repertoires appear to be structured into sets of reactivities that are organized into cliques—reactivities to particular antigens are correlated. (3) Autoantibody repertoires are organized as networks of reactivities in which certain key antigen reactivities dominate the network—the dominant antigen reactivities manifest a “causal” relationship to sets of other correlated reactivities. Thus, repertoires of autoantibodies in healthy subjects, the immunological homunculus, are structured in hierarchies of antigen reactivities.

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 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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. Cohen IR. The cognitive principle challenges clonal selection. Immunol Today 1992; 13:441–4. PMID: 1476598 doi:10.1016/0167-5699(92)90071-E

    Article  PubMed  CAS  Google Scholar 

  2. Cohen IR. Tending Adam’s Garden: Evolving the Cognitive Immune Self. London: Academic Press; 2000.

    Google Scholar 

  3. Cohen IR. Discrimination and dialogue in the immune system. Semin Immunol 2000; 12:215–9., discussion 57-344. PMID: 10910742 doi:10.1006/smim.2000.0234

    Article  PubMed  CAS  Google Scholar 

  4. Janeway CA, Travers P. Immunobiology: the Immune System in Health and Disease. New York: Garland Science; 2005.

    Google Scholar 

  5. Perelson AS. Immune network theory. Immunol Rev 1989; 110:5–36. PMID:2477327 doi:10.1111/j.1600-065X.1989.tb00025.x

    Article  PubMed  CAS  Google Scholar 

  6. Tauber AI. The Immune Self: Theory or Metaphor?: Cambridge University Press; 1994.

    Google Scholar 

  7. Cohen IR. Biomarkers, self-antigens and the immunological homunculus. J Autoimmun 2007; 29:246–9. PMID: 17888625 doi:10.1016/j.jaut.2007.07.016

    Article  PubMed  CAS  Google Scholar 

  8. Quintana FJ, Cohen IR. The natural autoantibody repertoire and autoimmune disease. Biomed Pharmacother 2004; 58:276–81. PMID:15194162 doi:10.1016/j.biopha.2004.04.011

    Article  PubMed  CAS  Google Scholar 

  9. Quintana FJ, Hagedorn PH, Elizur G et al. Functional immunomics: microarray analysis of IgG autoantibody repertoires predicts the future response of mice to induced diabetes. Proc Natl Acad Sci USA 2004; 101(Suppl 2):14615–21. PMID:15308778 doi:10.1073/pnas.0404848101

    Article  PubMed  CAS  Google Scholar 

  10. Quintana FJ, Merbl Y, Sahar E et al. Antigen-chip technology for accessing global information about the state of the body. Lupus 2006; 15:428–30. PMID: 16898177 doi:10.1191/09612033061u2328oa

    Article  PubMed  CAS  Google Scholar 

  11. Robinson WH. Antigen arrays for antibody profiling. Curr Opin Chem Biol 2006; 10:67–72. PMID: 16406767 doi:10.1016/j.cbpa.2005.12.028

    Article  PubMed  CAS  Google Scholar 

  12. Merbl Y, Zucker-Toledano M, Quintana FJ et al. Newborn humans manifest autoantibodies to defined self molecules detected by antigen microarray informatics. J Clin Invest 2007; 117:712–8. PMID: 17332892 doi:10.1172/JCI29943

    Article  PubMed  CAS  Google Scholar 

  13. Hanson LA, Korotkova M, Lundin S et al. The transfer of immunity from mother to child. Ann N Y Acad Sci 2003; 987:199–206. PMID: 12727640 doi:10.1111/j.1749-6632.2003.tb06049.x

    Article  PubMed  CAS  Google Scholar 

  14. Akilesh S, Christianson GJ, Roopenian DC et al. Neonatal FcR expression in bone marrow-derived cells functions to protect serum IgG from catabolism. J Immunol 2007; 179:4580–8. PMID: 17878355

    PubMed  CAS  Google Scholar 

  15. Madi A, Hecht I, Bransburg-Zabary S et al. Organization of the autoantibody repertoire in healthy newborns and adults revealed by system level informatics of antigen microarray data. Proc Natl Acad Sci USA 2009; 106:14484–9. PMID:19667184 doi:10.1073/pnas.0901528106

    Article  PubMed  CAS  Google Scholar 

  16. Baruchi I, Grossman D, Volman V et al. Functional holography analysis: simplifying the complexity of dynamical networks. Chaos 2006; 16:015112. PMID:16599778 doi:10.1063/1.2183408

    Article  PubMed  Google Scholar 

  17. Madi A, Friedman Y, Roth D et al. Genome holography: deciphering function-form motifs from gene expression data. PLoS ONE 2008; 3:e2708. PMID:18628959 doi:10.1371/journal.pone.0002708

    Article  PubMed  Google Scholar 

  18. Jerne NK. The natural-selection theory of antibody formation. Proc Natl Acad Sci USA 1955; 41:849–57. PMID:16589759 doi:10.1073/pnas.41.11.849

    Article  PubMed  CAS  Google Scholar 

  19. Jerne NK. Various basic problems of current immunology. Landarzt 1967; 43:1526–30. PMID: 5594622

    PubMed  CAS  Google Scholar 

  20. Jerne NK. Towards a network theory of the immune system. Ann Immunol (Paris) 1974; 125C:373–89. PMID:4142565

    CAS  Google Scholar 

  21. Mantegna RN, Stanley HE. An Introduction to Econophysics: Correlations and Complexity in Finance. Cambridge UK: Cambridge University Press; 2000.

    Google Scholar 

  22. Newman MEJ. The structure and function of complex networks. SIAM Rev 2003; 45:167–256 doi:10.1137/S003614450342480.

    Article  Google Scholar 

  23. Reka A, Barabasi AL. Statistical mechanics of complex networks. Rev Mod Phys 2002; 74:47–97 doi:10.1103/Rev Mod Phys.74.47. [AU1: Medline indexes “Rev Mod Phys” but cannot find a listing for reference 23 “Reka, Barabasi, 2002”. Please check the reference for accuracy.]

    Article  Google Scholar 

  24. Chazelle B. A minimum spanning tree algorithm with inverse-Ackermann type complexity. J ACM 2000; 47:1028–47 doi:10.1145/355541.355562.

    Article  Google Scholar 

  25. Graham RL, Hell P. On the history of the minimum spanning tree problem. IEEE Ann Hist Comput 1985; 7:43–57 doi:10.1109/MAHC. 1985.10011.

    Article  Google Scholar 

  26. Kruskal JB. On the shortest spanning subtree of a graph and the traveling salesman problem. Proc Am Math Soc 1956; 7:48–50 doi:10.1090/S0002-9939-1956-0078686-7.

    Article  Google Scholar 

  27. Xu Y, Olman V, Xu D. Minimum spanning trees for gene expression data clustering. Genome Inform 2001; 12:24–33. PMD: 11791221

    PubMed  CAS  Google Scholar 

  28. West DB. An Introduction to Graph Theory. Englewood Cliffs, NJ: Prentice-Hall; 2001.

    Google Scholar 

  29. Madi A, Kenett DY, Bransburg-Zabary S et al. Network theory analysis of antibody-antigen reactivity data: the immune trees at birth and adulthood. PLoS One 2011.

    Google Scholar 

  30. Lee U, Kim S. Classification of epilepsy types through global network analysis of scalp electroencephalograms. Phys Rev E Stat Nonlin Soft Matter Phys 2006; 73:ai]041920. PMID:16711849 doi:10.1103/Phys Rev E.73.041920

    Google Scholar 

  31. Madi A, Kenett DY, Bransburg-Zabary S et al. Analyses of antigen dependency networks unveil immune system reorganization between birth and adulthood. Chaos 2011.

    Google Scholar 

  32. Cohen IR. Natural autoantibodies might prevent autoimmune disease. In: Atlan H, editor. Berlin: Springer-Verlag; 1989.

    Google Scholar 

  33. Kenett DY, Tumminello M, Madi A et al. Dominating clasp of the financial sector revealed by partial correlation analysis of the stock market. PLoS ONE 2010; 5:e15032 DOI:doi:10.1371/journal.pone.0015032. PMID:21188140

    Article  PubMed  CAS  Google Scholar 

  34. Shapira Y, Kenett DY, Ben-Jacob E. The index cohesive effect on stock market correlations. Eur J Phys B 2009.

    Google Scholar 

  35. Sercarz EE. Driver clones and determinant spreading. J Autoimmun 2000; 14:275–7. PMID:10882052 doi:10.1006/jaut.2000.0380

    Article  PubMed  CAS  Google Scholar 

  36. Cohen IR. Real and artificial immune systems: computing the state of the body. Nat Rev Immunol 2007; 7:569–74. PMID: 17558422 doi:10.1038/nri2102

    Article  PubMed  CAS  Google Scholar 

  37. Cohen IR, Young DB. Autoimmunity, microbial immunity and the immunological homunculus. Immunol Today 1991; 12:105–10. PMID:2059311 doi:10.1016/0167-5699(91)90093-9

    Article  PubMed  CAS  Google Scholar 

  38. Nobrega A, Haury M, Grandien A et al. Global analysis of antibody repertoires. II. Evidence for specificity, self-selection and the immunological “homunculus” of antibodies in normal serum. Eur J Immunol 1993; 23:2851–9. PMID:8223861 doi:10.1002/eji.1830231119

    Article  PubMed  CAS  Google Scholar 

  39. Poletaev AB. The immunological homunculus (immunculus) in normal state and pathology. Biochemistry (Mosc) 2002; 67:600–8. PMID:12059783 doi:10.1023/A:1015514732179

    Article  CAS  Google Scholar 

  40. Hayakawa K, Asano M, Shinton SA et al. Positive selection of natural autoreactive B cells. Science 1999; 285:113–6. PMID: 10390361 doi:10.1126/science.285.5424.113

    Article  PubMed  CAS  Google Scholar 

  41. Avrameas S. Natural autoantibodies: from ‘horror autotoxicus’ to ‘gnothi seauton’. Immunol Today 1991; 12:154–9. PMID:1715166

    PubMed  CAS  Google Scholar 

  42. Cohen IR. The cognitive paradigm and the immunological homunculus. Immunol Today 1992; 13:490–4. PMID:1463581 doi:10.1016/0167-5699(92)90024-2

    Article  PubMed  CAS  Google Scholar 

  43. Quintana FJ, Cohen IR. The HSP 60 immune system network. Trends Immunol 2011; 32:89–95. PMID:21145789 doi:10.1016/j.it.2010.11.001

    Article  PubMed  CAS  Google Scholar 

  44. Burnet FM. A modification of Jerne’s theory of antibody production using the concept of clonal selection. CA Cancer J Clin 1976; 26:119–21.

    Article  PubMed  CAS  Google Scholar 

  45. Nossal GJ, Lederberg J. Antibody production by single cells. Nature 1958; 181:1419–20. PMID:13552693 doi:10.1038/1811419a0

    Article  PubMed  CAS  Google Scholar 

  46. Cohen IR, Cooke A. Natural autoantibodies might prevent autoimmune disease. Immunol Today 1986; 7:363–4 doi:10.1016/0167-5699(86)90026-5. [AU2: Medline indexes “Immunol Today” but cannot find a listing for reference 46 “Cohen, Cooke, 1986”. Please check the reference for accuracy.]

    Article  Google Scholar 

  47. Lacroix-Desmazes S, Mouthon L, Coutinho A et al. Analysis of the natural human IgG antibody repertoire: life-long stability of reactivities towards self antigens contrasts with age-dependent diversification of reactivities against bacterial antigens. Eur J Immunol 1995; 25:2598–604. PMID:7589132 doi:10.1002/eji. 1830250929

    Article  PubMed  CAS  Google Scholar 

  48. Lacroix-Desmazes S, Mouthon L, Kaveri SV et al. Stability of natural self-reactive antibody repertoires during aging. J Clin Immunol 1999; 19:26–34. PMID:10080102 doi:10.1023/A: 1020510401233

    Article  PubMed  CAS  Google Scholar 

  49. Mouthon L, Lacroix-Desmazes S, Nobrega A et al. The self-reactive antibody repertoire of normal human serum IgM is acquired in early childhood and remains conserved throughout life. Scand J Immunol 1996; 44:243–51. PMID:8795718 doi:10.1046/j. 1365-3083.1996.d01-306.x

    Article  PubMed  CAS  Google Scholar 

  50. de Boer RJ, Perelson AS. Size and connectivity as emergent properties of a developing immune network. J Theor Biol 1991; 149:381–424. PMID:2062103 doi:10.1016/S0022-5193(05)80313-3

    Article  PubMed  Google Scholar 

  51. Pandey RB. Growth and decay of a cellular population in a multicell immune network. J Phys Math Gen 1990; 23:4321 doi:10.1088/0305-4470/23/19/017.

    Article  Google Scholar 

  52. Zorzenon RM, Copelli M. Long term and short term effects of perturbations in an immune network model. Braz J Phys 2001; 33:628–33.

    Google Scholar 

  53. Parisi G. A simple model for the immune network. Proc Natl Acad Sci USA 1990; 87:429–33. PMID:2296597 doi:10.1073/pnas.87.1.429

    Article  PubMed  CAS  Google Scholar 

  54. Tauber AI. Moving beyond the immune self? Semin Immunol 2000; 12:241–8. PMID: 10910746 doi:10.1006/smim.2000.0237

    Article  PubMed  CAS  Google Scholar 

  55. Frankenstein Z, Alon U, Cohen IR. The immune-body cytokine network defines a social architecture of cell interactions. [r.]. Biol Direct 2006; 1:32. PMID:17062134 doi:10.1186/1745-6150-1-32

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Asaf Madi & Sharron Bransburg-Zabary

  2. School of Physics and Astronomy, Tel Aviv University, Tel Aviv, Israel

    Asaf Madi, Sharron Bransburg-Zabary, Dror Y. Kenett & Eshel Ben-Jacob

  3. The Center for Theoretical and Biological Physics, University of California San Diego, La Jolla, California, USA

    Eshel Ben-Jacob

  4. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

    Irun R. Cohen

Authors
  1. Asaf Madi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharron Bransburg-Zabary
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dror Y. Kenett
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eshel Ben-Jacob
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Irun R. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Irun R. Cohen .

Editor information

Editors and Affiliations

  1. Institute of Biochemistry, Swiss Federal Institute of Technology, ETH Hönggerberg, Zurich, Switzerland

    Hans U. Lutz

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Madi, A., Bransburg-Zabary, S., Kenett, D.Y., Ben-Jacob, E., Cohen, I.R. (2012). The Natural Autoantibody Repertoire in Newborns and Adults. In: Lutz, H.U. (eds) Naturally Occurring Antibodies (NAbs). Advances in Experimental Medicine and Biology, vol 750. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3461-0_15

Download citation

Publish with us

Policies and ethics

Search

Navigation