SpringerLink
Log in

Hypotheses of the origin of natural antibodies: A glycobiologist’s opinion

  • Review
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

It is generally accepted that the generation of antibodies proceeds due to immunization of an organism by alien antigens, and the level and affinity of antibodies are directly correlated to the presence of immunogen. At the same time, vast experimental material has been obtained providing evidence of antibodies whose level remains unchanged and affinity is constant during a lifetime. In contrast to the first, adaptive immunoglobulins, the latter are named natural antibodies (nAbs). The nAbs are produced by B1 cells, whereas adaptive Abs are produced by B2. This review summarizes general data on nAbs and presents in more detail data on antigens of carbohydrate origin. Hypotheses on the origin of nAbs and their activation mechanisms are discussed. We present our thoughts on this matter supported by our experimental data on nAbs to glycans.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

DAMP:

damage-associated molecular patterns

mAbs:

monoclonal antibodies

MAMP:

microorganism-associated molecular patterns

nAbs:

natural antibodies

TACA:

tumor-associated carbohydrate antigens

References

  1. Winau, F., Westphal, O., and Winau, R. (2004) Paul Ehrlich- in search of the magic bullet, Microbes Infect., 68, 786–789.

    Google Scholar 

  2. Roit, A. (1991) Fundamentals of Immunology [Russian translation], Mir, Moscow.

  3. Abelev, G. I. (1996) Fundamentals of immunity, Soros Educat. J., 5, 4–10.

    Google Scholar 

  4. Landsteiner, K., and Philip Miller, C. Ph., Jr. (1925) Serological studies on the blood of the primates. II. The blood groups in anthropoids apes, J. Exp. Med., 42, 853–862.

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Landsteiner, K., and Levine, P. (1927) Further observations on individual differences of human blood, Proc. Soc. Exp. Biol., 24, 941–942.

    CAS  Google Scholar 

  6. Burnet, F. M. (1976) A modification of Jerne’s theory of antibody production using the concept of clonal selection, CA Cancer J. Clin., 26, 119–121.

    CAS  PubMed  Google Scholar 

  7. Silverstein, A. M. (2009) A History of Immunology, Academic Press, N. Y, 2nd Edn.

  8. Burnet, F. M. (1978) Clonal selection and after, in Theoretical Immunology (Bell, G. I., Perelson, A. S., and Pimbley, G. H., Jr., eds.) Marcel Dekker Inc., pp. 63–85.

    Google Scholar 

  9. Yarilin, A. A. (2010) Immunology [in Russian], GEOTARMedia, Moscow.

  10. Janeway, Ch. A., Travers, P., Jr., Walport, M., and Shlomchik, M. J. (2001) The Immune System in Health and Disease. Immunobiology, 5th Edn., Garland Science, N. Y.

  11. Schatz, D. G., Oettinger, M. A., and Baltimore, D. (1989) The V(D)J recombination activating gene, RAG-1, Cell, 59, 1035–1048.

    CAS  PubMed  Google Scholar 

  12. Lutz, H. U. (2012) Naturally occurring antibodies (nAbs), Adv. Exp. Med. Biol., 750, vii-x, p. 267.

    Google Scholar 

  13. Hayakawa, K., and Hardy, R. R. (2000) Development and function of B-1 cells, Curr. Opin. Immunol., 12, 346–353.

    CAS  PubMed  Google Scholar 

  14. Guilbert, B., Digheiro, G., and Avrameas, S. (1982) Naturally occurring antibodies against nine common antigens in human sera, J. Immunol., 128, 2779–2787.

    CAS  PubMed  Google Scholar 

  15. Zhou, Z-H., Tzioufas, G. A., and Notkins, A. L. (2007) Properties and function of polyreactive antibodies and polyreactive antigen-binding B cells, J. Autoimmun., 29, 219–228.

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Cohen, I. (2013) Autoantibody repertoires, natural biomarkers, and system controllers, Trends Immunol., 34, 620–625.

    CAS  PubMed  Google Scholar 

  17. Daniels, G. (2003) Human Blood Groups, 3rd Edn., Blackwell Science, Oxford.

  18. Gershvin, M. E., Meroni, P. L., and Shoenfeld, Y (2006) Autoantibodies, 2nd Edn., Elsevier Science.

  19. Avrameas, S. (1991) Natural autoantibodies: from “horror autotoxicus” to “gnothiseauton”, Immunol. Today, 12, 154–159.

    CAS  PubMed  Google Scholar 

  20. Boes, M. (2000) Role of natural and immune IgM antibodies in immune responses, Mol. Immunol., 37, 1141.1149.

    CAS  PubMed  Google Scholar 

  21. Zhou, Z-H., Zhang, Y., Hu, Y-F., Wahl, L. M., Cisar, J. O., and Notkins, A. L. (2007) The broad antibacterial activity of the natural antibody repertoire is due to polyreactive antibodies, Cell Host Microbe, 1, 51–61.

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Racine, R., and Winslow, G. M. (2009) IgM in microbial infections: taken for granted? Immunol. Lett., 125, 79–85.

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Ochsenbein, A. F., Fehr, T, Lutz, C., Suter, M., Brombacher, F., Hengartner, H., and Zinkernagel, R. M. (1999) Control of early viral and bacterial distribution and disease by natural antibodies, Science, 286, 2156–2159.

    CAS  PubMed  Google Scholar 

  24. Ochsenbein, A. F., and Zinkernagel, R. M. (2000) Natural antibodies and complement link innate and acquired immunity, Immunol. Today, 21, 624–630.

    CAS  PubMed  Google Scholar 

  25. Baumgarth, N., Tung, J. W., and Herzenberg, L. A. (2005) Inherent specificities in natural antibodies: a key to immune defense against pathogen invasion, Springer Semin. Immun., 26, 347–362.

    CAS  Google Scholar 

  26. Chou, M.-Y., Fogelstrand, L., Hartvigsen, K., Hansen, L. F., Woelkers, D., Shaw, P. X., Choi, J., Perkmann, T, Backhed, F., Miller, Y I., Horkko, S., Corr, M., Witztum, J. L., and Binder, C. J. (2009) Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans, J. Clin. Invest., 199, 1335–1349.

    Google Scholar 

  27. Lutz, H. U. (2007) Homeostatic roles of naturally occurring antibodies: an overview, J. Autoimmun., 29, 287–294.

    CAS  PubMed  Google Scholar 

  28. Binder, C. J., Shaw, P. X., Chang, M.-K., Boullier, A., Hartvigsen, K., Horkko, S., Miller, Y I., Woelkers, D. A., Corr, M., and Witztum, J. L. (2005) The role of natural antibodies in atherogenesis, J. Lipid Res., 46, 1353–1363.

    CAS  PubMed  Google Scholar 

  29. Tsiantoulas, D., Gruber, S., and Binder, C. J. (2013) B-1 cell immunoglobulin directed against oxidation-specific epitopes, Front. Immunol., 9, 415..

    Google Scholar 

  30. Galili, U. (2004) Immune response, accommodation, and tolerance to transplantation carbohydrate antigens, Transplantation, 78, 1093–1098.

    CAS  PubMed  Google Scholar 

  31. Hayakawa, K., Hardy, R. R., and Herzenberg, L. A. (1986) Peritoneal Ly-1 B cells: genetic control, autoantibody production, increased lambda light chain expression, Eur. J. Immunol., 16, 450–456.

    CAS  PubMed  Google Scholar 

  32. Bendelac, A., Bonneville, M., and Kearney, J. F. (2001) Autoreactivity by design: innate B and T lymphocytes, Nature Rev. Immunol., 1, 177–186.

    CAS  Google Scholar 

  33. Hayakawa, K., Asano, M., Shinton, S. A., Gui, M., Allman, D., Stewart, C. L., Silver, J., and Hardy, R. R. (1999) Positive selection of natural autoreactive B cells, Science, 285, 113–116.

    CAS  PubMed  Google Scholar 

  34. Hao, Z., and Rajewsky, K. (2001) Homeostasis of peripheral B cells in the absence of B cell influx from the bone marrow, J. Exp. Med., 194, 1151–1163.

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Itakura, A., Szczepanik, M., Campos, R. A., Paliwal, V., Majewska, M., Matsuda, H., Takatsu, K., and Askenase, P. W. (2005) An hour after immunization peritoneal B-1 cells are activated to migrate to lymphoid organs where within 1 day they produce IgM antibodies that initiate elicitation of contact sensitivity, J. Immunol., 175, 7170–7178.

    CAS  PubMed  Google Scholar 

  36. Abelev, G. L. (1971) Alpha-fetoprotein in ontogenesis and its association with malignant tumors, Adv. Cancer Res., 14, 295–358.

    CAS  PubMed  Google Scholar 

  37. Barak, V. (2006) Tumor Biology. Tumor Markers, Tumor Targeting and Translational Cancer Research (Stigbrand, T, ed.) Karger Medical and Scientific Publishers, N.Y, p. 116.

    Google Scholar 

  38. Armenti, V. T, Moritz, M. J., Cardonick, E. H., and Davison, J. M. (2002) Immunosuppression in pregnancy: choices for infant and maternal health, Drugs, 62, 2361.2375.

    CAS  PubMed  Google Scholar 

  39. Elliott, A. B., and Chakravarty, E. F. (2010) Immunosuppressive medications during pregnancy and lactation in women with autoimmune diseases, Womens Health (London), 6, 431–440.

    Google Scholar 

  40. Badami, K. G., Vanhecke, C., and Bingham, J. (2009) Maternal IgM anti-D, borderline foetal Doppler middle cerebral artery velocities and absent neonatal hemolysis, Transfus. Med., 19, 146–147.

    CAS  PubMed  Google Scholar 

  41. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (2002) Molecular Biology of the Cell, 4th Edn., Garland Science, N.Y.

  42. Mackie, R. I., Sghir, A., and Gaskins, H. R. (1999) Developmental microbial ecology of the neonatal gastrointestinal tract, Am. J. Clin. Nutr., 69, 1035–1045.

    Google Scholar 

  43. Mariat, D., Firmesse, O., Levenez, F., Guimaraes, V. D., Sokol, H., Dore, J., Corthier, G., and Furet, J.-P. (2009) The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age, BMC Microbiol., 9, 1–6.

    Google Scholar 

  44. Ley, R. E., Lozupone, C. A., Hamady, M., Knight, R., and Gordon, J. I. (2008) Worlds within worlds: evolution of the vertebrate gut microbiota, Nature Rev. Microbiol., 6, 7767–7788.

    Google Scholar 

  45. Dethlefsen, L., Eckburg, P. B., Bik, E. M., and Relman, D. A. (2006) Assembly of the human intestinal microbiota, Trends Ecol. Evol., 21, 517–523.

    PubMed  Google Scholar 

  46. Lanning, D. K., Rhee, K. J., and Knight, K. L. (2005) Intestinal bacteria and development of the B-lymphocyte repertoire, Trends Immunol., 26, 419–425.

    CAS  PubMed  Google Scholar 

  47. Bulatova, E. M., and Bogdanova, N. M. (2010) The importance of the intestinal microbiota and probiotics in generation of immune response and health of a child, Vorp. Sovrem. Pediatr., 6, 37–44.

    Google Scholar 

  48. Berg, R. D. (1999) Bacterial translocation from the gastrointestinal tract, Adv. Exp. Med. Biol., 473, 11–30.

    CAS  PubMed  Google Scholar 

  49. Kelly, D., King, T., and Aminov, R. (2007) Importance of microbial colonization of the gut in early life to the development of immunity, Mutat. Res., 622, 58–69.

    CAS  PubMed  Google Scholar 

  50. Cash, H. L., and Hooper, L. V. (2005) Commensal bacteria shape intestinal immune system development, ASM News, 71, 77–83.

    Google Scholar 

  51. Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L., and Gordon, J. I. (2011) Human nutrition, the gut microbiome and the immune system, Nature, 474, 327–336.

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Otter, J. A., Vickery, K., Walker, J. T, de Lancey, P. E., Stoodley, P., Goldenberg, S. D., Salkeld, J. A., Chewins, J., Yezli, S., and Edgeworth, J. D. J. (2015) Surface-attached cells, biofilms and biocide susceptibility: implications for hospital cleaning and disinfection, Hosp. Infect., 89, 16–27.

    CAS  Google Scholar 

  53. Leid, J. G., Willson, C. J., Shirtliff, M. E., Hassett, D. J., Parsek, M. R., and Jeffers, A. K. (2005) The exopolysaccharide alginate protects Pseudomonas aeruginosa biofilm bacteria from IFN-gamma-mediated macrophage killing, J. Immunol., 175, 7512–7518.

    CAS  PubMed  Google Scholar 

  54. Suzuki, K., Ha, S-A., Tsuji, M., and Fagarasan, S. (2007) Intestinal IgA synthesis: a primitive form of adaptive immunity that regulates microbial communities in the gut, Semin. Immunol., 19, 127–135.

    CAS  PubMed  Google Scholar 

  55. Cerutti, A., and Rescigno, M. (2008) The biology of intestinal immunoglobulin A responses, Immunity, 28, 740–750.

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Tsuji, M., Suzuki, K., Kinoshita, K., and Fagarasan, S. (2008) Dynamic interactions between bacteria and immune cells leading to intestinal IgA synthesis, Semin. Immunol., 20, 59–66.

    CAS  PubMed  Google Scholar 

  57. Deplancke, B., and Gaskins, H. R. (2001) Microbial modulation of innate defense: goblet cells and the intestinal mucus layer, Am. J. Clin. Nutr., 73, 1131–1141.

    Google Scholar 

  58. Frederiksen, R. F., Paspaliari, D. K., Larsen, T, Storgaard, B. G., Larsen, M. H., Ingmer, H., Palcic, M. M., and Leisner, J. J. (2013) Bacterial chitinases and chitin-binding proteins as virulence factors, Microbiology, 159, 833–847.

    CAS  PubMed  Google Scholar 

  59. Langhendries, J. P. (2005) Early bacterial colonization of the intestine: why it matters, Ital. J. Pediatr., 31, 360–369.

    Google Scholar 

  60. Wold, A. E., and Adlerberth, I. (2000) Breast feeding and the intestinal microflora of the infant-implications for protection against infectious diseases, Adv. Exp. Med. Biol., 478, 77–93.

    CAS  PubMed  Google Scholar 

  61. Lu, L., and Walker, W A. (2001) Pathologic and physiologic interactions of bacteria with the gastrointestinal epithelium, Am. J. Clin. Nutr., 73, 1124–1130.

    Google Scholar 

  62. Panigrahi, P., Parida, S., Pradhan, L., Mohapatra, S. S., Misra, P. R., Johnson, J. A., Chaudhry, R., Taylor, S., Hansen, N. I., and Gewolb, I. H. (2008) Long-term colonization of a Lactobacillus plantarum synbiotic preparation in the neonatal gut, J. Pediatr. Gastroenterol. Nutr., 47, 4553..

    Google Scholar 

  63. Abreu, M. T (2010) Toll-like receptor signaling in the intestinal epithelium: how bacterial recognition shapes intestinal function, Nature Rev. Immunol., 10, 131–144.

    CAS  Google Scholar 

  64. Guarner, F., and Malagelada, J.-R. (2003) Gut flora in health and disease, Lancet, 361, 512–519.

    PubMed  Google Scholar 

  65. Balzan, S., Almeida Quadros, A., de Cleva, R., Zilberstein, B., and Cecconello, I. (2007) Bacterial translocation: overview of mechanisms and clinical impact, J. Gastroenterol. Hepatol., 22, 464–471.

    CAS  PubMed  Google Scholar 

  66. Springer, G. F., Horton, R. E., and Forbes, M. (1959) Origin of antihuman blood group B agglutinins in germfree chicks, J. Exp. Med., 110, 221–244.

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Springer, G. F. (1971) Blood-group and Forssman antigenic determinants shared between microbes and mammalian cells, Prog. Allergy, 15, 9–77.

    CAS  PubMed  Google Scholar 

  68. Wagner, R. D. (2008) Effects of microbiota on GI health: gnotobiotic research, Adv. Exp. Med. Biol., 635, 41–56.

    PubMed  Google Scholar 

  69. De Filippo, C., Cavalieri, D., Di Paola, M., Ramazzotti, M., Poullet, J. B., Massart, S., Collini, S., Pieraccini, G., and Lionetti, P (2010) Impact of diet in sha** gut microbiota revealed by a comparative study in children from Europe and rural Africa, Proc. Natl. Acad. Sci. USA, 107, 14691–14696.

    PubMed Central  PubMed  Google Scholar 

  70. Bischof, S. C. (2011) “Gut health”: a new objective in medicine? BMC Medicine, 9, 1–14.

    Google Scholar 

  71. Bos, N. A., Kimura, H., Meeuwsen, C. G., De Vi sser, H., Ha zenberg, M. P., Wostmannn, B. S., Pleasants, J. R., Benner, B., and Marcus, D. M. (1980) Serum immunoglobulin levels and naturally occurring antibodies against carbohydrate antigens in germ-free BALB/c mice fed chemically defined ultrafiltered diet, Eur. J. Immunol., 19, 2335–2339.

    Google Scholar 

  72. Kozakova, H., Kolinska, J., Lojda, Z., Rehakova, Z., Sinkora, J., Zakostelecka, M., Splichal, I., and Tlaskalova- Hogenova, E. (2006) Effect of bacterial monoassociation on brush-border enzyme activities in ex-germ-free piglets: comparison of commensal and pathogenic Escherichia coli strains, Microbes Infect., 8, 2629–2639.

    CAS  PubMed  Google Scholar 

  73. Butler, J. E., Sun, J., Weber, P, Navarro, P., and Francis, D. (2000) Antibody repertoire development in fetal and newborn piglets. III. Colonization of the gastrointestinal tract selectively diversifies the preimmune repertoire in mucosal lymphoid tissues, Immunology, 100, 119–130.

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Coutinho, A., Kazatchkine, M. D., and Avrameas, S. (1995) Natural autoantibodies, Curr. Opin. Immunol., 7, 812–818.

    CAS  PubMed  Google Scholar 

  75. Nores, G. A., Lardone, R. D., Comin, R., Alaniz, M. E., Moyano, A. L., and Irazoqui, F. J. (2008) Anti-GM1 antibodies as a model of the immune response to self-glycan, BBA, 1780, 538–545.

    CAS  PubMed  Google Scholar 

  76. Danussi, C., Coslovi, A., Campa, C., Mucignat, M. T., Spessotto, P., Uggeri, F., Paoletti, S., and Colombatti, A. (2009) A newly generated functional antibody identifies Tn antigen as a novel determinant in the cancer cell-lymphatic endothelium interaction, Glycobiology, 19, 1056–1067.

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Mouthon, L., Haury, M., Lacroix-Desmazes, S., Barreau, C., Coutinho, A., and Kazatchkine, M. D. (1995) Analysis of the normal human IgG antibody repertoire, J. Immunol., 154, 5769–5778.

    CAS  PubMed  Google Scholar 

  78. Hayakawa, K., and Hardy, R. R. (2005) Development of B cells producing natural autoantibodies to thymocytes and senescent erythrocytes, Springer Semin. Immun., 26, 363–375.

    Google Scholar 

  79. Lacroix-Desmazes, S., Srini, U., Kaveri, V., Mouthon, L., Ayouba, A., Malanchere, E., Coutinho, A., and Kazatchkine, M. D. (1998) Self-reactive antibodies natural autoantibodies in healthy individuals, J. Immunol. Methods, 216, 117–137.

    CAS  PubMed  Google Scholar 

  80. Pancer, Z., and Cooper, M. D. (2006) The evolution of adaptive immunity, Annu. Rev. Immunol., 24, 497–518.

    CAS  PubMed  Google Scholar 

  81. Servettaz, A., Guilpain, P, Tamas, N., Kaveri, S. V., Camoin, L., and Mouthon, L. (2008) Natural antiendothelial cell antibodies, Autoimmun. Rev., 7, 426–430.

    CAS  PubMed  Google Scholar 

  82. Ronda, N., Haury, M., Nobrega, A., Kaveri, S. V., Coutlnho, A., and Kazatchkine, M. D. (1994) Analysis of natural and disease-associated autoantibody repertoires: anti-endothelial cell IgG autoantibody activity in the serum of healthy individuals and patients with systemic lupus erythematosus, Int. Immunol., 6, 1651–1660.

    CAS  PubMed  Google Scholar 

  83. Pashov, A., Kenderov, A., Kyurkchiev, S., Kehayov, I., Hristova, S., Lacroix-Desmazes, S., Giltiay, N., Varamballi, S., Kazatchkine, M. D., and Kaveri, S. V. (2002) Autoantibodies to heat shock protein 90 in the human natural antibody repertoire, Int. Immunol., 14, 453–461.

    CAS  PubMed  Google Scholar 

  84. Yadin, O., Sarov, B., Naggan, L., Slor, H., and Shoenfeld, Y. (1989) Natural autoantibodies in the serum of healthy women- a five-year follow-up, Clin. Exp. Immunol., 75, 402–406.

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Pierson, R. N., Loyd, J. E., Goodwin, A., Majors, D., Dummer, J. S., Mohacsi, P., Wheeler, A., Bovin, N., Miller, G. G., Olson, S., Johnson, J., Rieben, R., and Azimzadeh, A. (2002) Successful management of an ABOmismatched lung allograft using antigen-specific immunoadsorption, complement inhibition, and immunomodulatory therapy, Transplantation, 15, 79–84.

    Google Scholar 

  86. Wardemann, H., Yurasov, S., Schaefer, A., Young, J. W, Meffre, E., and Nussenzweig, M. C. (2003) Predominant autoantibody production by early human B cell precursors, Science, 301, 1374–1377.

    CAS  PubMed  Google Scholar 

  87. Quintana, F. J., and Cohen, I. R. (2004) The natural autoantibody repertoire and autoimmune disease, Biomed. Pharmacother., 58, 276–281.

    CAS  PubMed  Google Scholar 

  88. Oka, Y, Hirabayashi, Y, Ikeda, T, Fujii, H., Ishii, T, and Harigae, H. (2011) A single-stranded DNA-cross-reactive immunogenic epitope of human homocysteine-inducible endoplasmic reticulum protein, Scand. J. Immunol., 74, 296–303.

    CAS  PubMed  Google Scholar 

  89. Allos, B. M., Lippy, F. T, Carlsen, A., Washburn, R. G., and Blaser, M. J. (1998) Campylobacter jejuni strains from patients with Guillain-Barre syndrome, Emerg. Infect. Dis., 4, 263–268.

    CAS  PubMed Central  PubMed  Google Scholar 

  90. Thornton, C. A., and Morgan, G. (2009) Innate and adaptive immune pathways to tolerance, Nestle Nutr. Workshop Ser. Pediatr. Program., 64, 45–57.

    CAS  PubMed  Google Scholar 

  91. Janeway, C. A., and Medzhitov, R. (2002) Innate immune recognition, Annu. Rev. Immunol., 20, 197–216.

    CAS  PubMed  Google Scholar 

  92. Baldus, S. E., Hanisch, F. G., Kotlarek, G. M., Zirbes, T K., Thiele, J., Isenberg, J., Karsten, U. R., Devine, P. L., and Dienes, H. P. (1998) Coexpression of MUC-1 mucin peptide core and the Thomsen-Friedenreich antigen in colorectal neoplasms, Cancer, 82, 1019–1027.

    CAS  PubMed  Google Scholar 

  93. Gorshkova, T. A. (2007) The Plant Cell Wall as a Dynamic System [in Russian], Nauka, Moscow, p. 426.

    Google Scholar 

  94. Bovin, N. V. (2013) Natural antibodies to glycans, Biochemistry (Moscow), 78, 786–797.

    CAS  Google Scholar 

  95. Knirel, Y. A., Gabius, H.-J., Blixt, O., Rapoport, E. M., Khasbiullina, N. R., Shilova, N. V., and Bovin, N. V. (2014) Human tandem-repeat-type galectins bind bacterial non-ßGal polysaccharides, Glycoconj. J., 31, 7–12.

    CAS  PubMed  Google Scholar 

  96. Hakomori, S. (2001) The glycosynapse, PNAS, 99, 2252.32.

    Google Scholar 

  97. Hakomori, S., and Handa, K. (2015) GM3 and cancer, Glycoconj. J., 32, 1–8.

    CAS  PubMed  Google Scholar 

  98. Todeschini, A. R., Dos Santos, J. N., Handa, K., and Hakomori, S. (2008) Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway, Proc. Natl. Acad. Sci. USA, 105, 1925–1930.

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Di Virgilio, F. (2013) The therapeutic potential of modifying inflammasomes and NOD-like receptors, Pharmacological, 65, 872–905.

    CAS  Google Scholar 

  100. Mills, K. H. (2011) TLR-dependent T cell activation in autoimmunity, Nature Rev. Immunol., 11, 807–822.

    CAS  Google Scholar 

  101. Gellert, M. (1997) Recent advances in understanding V(D)J recombination, Adv. Immunol., 64, 39–64.

    CAS  PubMed  Google Scholar 

  102. Hennings, L., Artaud, C., Jousheghany, F., Monzavi- Karbassi, B., Pashov, A., and Kieber-Emmons, T (2011) Carbohydrate mimetic peptides augment carbohydratereactive immune responses in the absence of immune pathology, Cancers (Basel), 3, 4151–4169.

    CAS  Google Scholar 

  103. Avrameas, S., Dighiero, G., Lymberi, P., and Guilbert, B. (1983) Studies on natural antibodies and autoantibodies, Ann. Immunol. (Paris), 134, 103–113.

    Google Scholar 

  104. Stahl, D., Lacroix-Desmazes, S., Mouthon, L., Kaveri, S. V., and Kazatchkine, M. D. (2000) Analysis of human selfreactive antibody repertoires by quantitative immunoblotting, J. Immunol. Methods, 240, 1–14.

    CAS  PubMed  Google Scholar 

  105. Madi, A., Kenett, D. Y, Bransburg-Zabary, S., Merbl, Y, Quintana, F. J., Boccaletti, S., Tauber, A. I., Cohen, I. R., and Ben-Jacob, E. (2011) Analyses of antigen dependency networks unveil immune system reorganization between birth and adulthood, Chaos, 21, 1–11.

    Google Scholar 

  106. Springer, G. F. (1971) Blood-group and Forssman antigenic determinants shared between microbes and mammalian cells, Prog. Allergy, 15, 9–77.

    CAS  PubMed  Google Scholar 

  107. Bovin, N., Obukhova, P., Shilova, N., Rapoport, E., Popova, I., Navakouski, M., Unverzagt, C., Vuskovic, M., and Huflejt, M. (2012) Repertoire of human natural antiglycan immunoglobulins. Do we have auto-antibodies? Biochim. Biophys. Acta, 1820, 1373–1382.

    CAS  PubMed  Google Scholar 

  108. Obukhova, P., Piskarev, V., Severov, V., Pazynina, G., Tuzikov, A., Navakouski, M., Shilova, N., and Bovin, N. (2011) Profiling of serum antibodies with printed glycan array: room for data misinterpretation, Glycocon. J., 28, 501–505.

    CAS  Google Scholar 

  109. Tupitsyn, N. N., Udalova, Y. A., Galanina, O. E., Kadagidze, Z. G., Borovkova, N. B., Podolsky, V. V., Shinkarev, S. A., Gadetskaya, N. A., Letyagin, V. P., Obukhova, P. S., Shilova, N. V., Subbotina, A. A., and Bovin, N. V. (2009) Tumor-associated glycan Lewis C in breast cancer, Hematopoiesis Immunol., 2, 45–54.

    Google Scholar 

  110. Hakomori, S. (1984) Tumor-associated carbohydrate antigens, Annu. Rev. Immunol., 2, 103–126.

    CAS  PubMed  Google Scholar 

  111. Lloyd, K. O. (1991) Humoral immune responses to tumor-associated carbohydrate antigens, Semin. Cancer Biol., 2, 421–431.

    CAS  PubMed  Google Scholar 

  112. Livingston, P. O. (1995) Augmenting the immunogenicity of carbohydrate tumor antigens, Semin. Cancer Biol., 2, 357–366.

    Google Scholar 

  113. Springer, G. F. (1984) T and Tn, general carcinoma autoantigens, Science, 224, 1198–1206.

    CAS  PubMed  Google Scholar 

  114. Huflejt, M. E., Vuskovic, M., Vasiliu, D., Xu, H., Obukhova, P., Shilova, N., Tuzikov, A., Galanina, O., Arun, B., Lu, K., and Bovin, N. V. (2009) Anti-carbohydrate antibodies of normal sera: findings, surprises and challenges, Mol. Immunol., 46, 3037–3049.

    CAS  PubMed  Google Scholar 

  115. Jacob, F., Goldstein, D. R., Huflejt, M., Bovin, N., Pochechueva, T, Spengler, M., Caduff, R., Fink, D., and Heinzelmann-Schwarz, V. (2012) Serum antiglycan antibody detection of nonmucinous ovarian cancers by using a printed glycan array, Int. J. Cancer, 130, 1381–1346.

    Google Scholar 

  116. Bovin, N. V., and Huflejt, M. E. (2008) Unlimited glycochip, Trends Glycosci. Glycotechnol., 20, 245–258.

    CAS  Google Scholar 

  117. Cheng, H., Yang, Z., Estabrook, M. M., John, C. M., Jarvis, G. A., McLaughlin, S., and Griffiss, M. (2011) Human lipopolysaccharide IgG that prevents endemic meningococcal disease recognizes an internal lacto- N-neotetraose structure, J. Biol. Chem., 286, 4362–243633.

    Google Scholar 

  118. Kurtenkov, O., Miljukhina, L., Smorodin, J., Klaamas, K., Bovin, N., Ellamaa, M., and Chuzmarov, V. (1999) Natural IgM and IgG antibodies to Thomsen- Friedenreich (T) antigen in serum of patients with gastric cancer and blood donors, Acta Oncol., 38, 939–943.

    CAS  PubMed  Google Scholar 

  119. Lekakh, I. V., Bovin, N. V., Bezyaeva, G. P., and Poverenny, A. M. (2001) Natural hidden autoantibodies react with negatively charged carbohydrates and xenoantigen Bdi, Biochemistry (Moscow), 66, 205–210.

    Google Scholar 

  120. Krenn, V., von Landenberg, P., Wozniak, E., Kissler, C., Hermelink, H. K., Zimmermann, U., and Vollmers, H. P. (1995) Efficient immortalization of rheumatoid synovial tissue B-lymphocytes. A comparison between the techniques of electric field-induced and PEG fusion, Hum. Antibodies Hybridomas, 6, 47–51.

    CAS  PubMed  Google Scholar 

  121. Anthony, R. M., and Ravetch, J. V. (2010) A novel role for the IgG Fc glycan: the anti-inflammatory activity of sialylated IgG Fcs, J. Clin. Immunol., 30, 9–14.

    Google Scholar 

  122. Stadlmann, J., Pabst, M., and Altmann, F. (2010) Analytical and functional aspects of antibody sialylation, J. Clin. Immunol., 30, 15–19.

    PubMed Central  Google Scholar 

  123. Wassenaar, T. M., and Panigrahi, P. (2014) Is a fetus develo** in a sterile environment? Lett. Appl. Microbiol., 59, 572–579.

    CAS  PubMed  Google Scholar 

  124. Aagaard, K. M. (2014) Author response to comment on “the placenta harbors a unique microbiome”, Sci. Transl. Med., 6, 254–256.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia

    N. R. Khasbiullina & N. V. Bovin

Authors
  1. N. R. Khasbiullina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. V. Bovin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. R. Khasbiullina.

Additional information

To whom correspondence should be addressed.

Original Russian Text © N. R. Khasbiullina, N. V. Bovin, 2015, published in Biokhimi^a, 2015, Vol. 80, No. 7, pp. 980-997.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khasbiullina, N.R., Bovin, N.V. Hypotheses of the origin of natural antibodies: A glycobiologist’s opinion. Biochemistry Moscow 80, 820–835 (2015). https://doi.org/10.1134/S0006297915070032

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297915070032

Keywords

Search

Navigation