Ukr.Biochem.J. 2020; Volume 92, Issue 4, Jul-Aug, pp. 35-44

doi: https://doi.org/10.15407/ubj92.04.035

Both maternal and newborn IgMs inhibit influenza virus-induced hemagglutination in vitro

02.09.2020   Uncategorized   No comments

A. P. Pogribna1*, M. Y. Grom2, I. V. Sokol3,
V. Berestoviy3, D. O. Govsieiev4

1Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv;
2Research Institute “Zhyttya”, Kyiv, Ukraine;
3Bogomolets National Medical University, Kyiv, Ukraine;
4Kyiv City Maternity Hospital No 5, Ukraine;
*e-mail: pogr@ukr.net

Received: 16 October 2019; Accepted: 15 May 2020

Most serum immunoglobulins M (IgMs) are “natural IgMs”, which are produced apparently spontaneously without exogenous antigenic or microbial stimuli. The IgMs are the first immunoglobulins expressed in the human fetus, and the maternal IgM do not cross the placenta in the normal conditions. We currently lack a clear understanding of the molecular basis for immunological differences or identities of IgM repertoires between adults and neonates, so we have tried to apply a simple and illustrative method to compare the properties of such IgM antibodies. This study was undertaken to compare the abilities of pairs of maternal and newborn highly-purified total serum IgM antibodies to block influenza virus agglutinins. We collected ten pairs of serum samples from cord blood of apparently healthy newborns and venous blood of their mothers. The highly purified total IgM antibodies were obtained by sequential salt fractionation and affinity chromatography. The effect of IgM antibodies on virus hemagglutinin interaction with erythrocytes was evaluated by hemagglutination reaction using influenza virus vaccine. According to the titer of influenza hemagglutinins, the IgM antibodies of newborns decreased hemagglutination of erythrocytes two to four times more efficiently compared to IgM antibodies of their mothers (8 out of 10 cases). Our results demonstrate that serum IgMs of newborns are able to interfere with influenza virus agglutinins even more efficiently than those of adults. These data may be useful for better understanding of immune system development in newborns.

Keywords: , , ,

References:

  1. Walkovich K, Connelly JA. Primary Immunodeficiency in the Neonate: Early Diagnosis and Management. Semin Fetal Neonatal Med. 2016;21(1):35-43. PubMed, CrossRef
  2. Kwan A, Puck JM. History and current status of newborn screening for severe combined immunodeficiency. Semin Perinatol. 2015;39(3):194-205. PubMed, PubMedCentral, CrossRef
  3. van Furth R, Schuit HR, Hijmans W. The Immunological Development of the Human Fetus. J Exp Med. 1965;122(6):1173-1188. PubMed, PubMedCentral, CrossRef
  4. Ozdemir SA,  Ozer EA, Kose S, Ilhan O, Ozturk C, Sutcuoglu S. Reference values of serum IgG and IgM levels in preterm and term newborns. J Matern Fetal Neonatal Med. 2016;29(6):972-976. PubMed, CrossRef
  5. Pineda-Martínez S, Hernández-Islas JL, Escobedo-Torres MP, Paredes-Alonzo IE, López-Candiani C, Correa D, Vela-Amieva M. Immunoglobulin concentrations in plasma and saliva during the neonatal period. Pediatr Neonatol. 2016;57(3):213-218. PubMed, CrossRef
  6. Díaz-Zaragoza M, Hernández-Ávila R, Viedma-Rodríguez R, Arenas-Aranda D, Ostoa-Saloma P. Natural and Adaptive IgM Antibodies in the Recognition of Tumor-Associated Antigens of Breast Cancer (Review). Oncol Rep. 2015;34(3):1106-1114. PubMed, PubMedCentral, CrossRef
  7. Klimovich VB. IgM and Its Receptors: Structural and Functional Aspects. Biochemistry (Mosc). 2011 May;76(5):534-549. PubMed, CrossRef
  8. Casali P, Schettino EW. Structure and Function of Natural Antibodies. Curr Top Microbiol Immunol. 1996;210:167-179. PubMed, CrossRef
  9. Coutinho A, Kazatchkine MD, Avrameas S. Natural Autoantibodies. Curr Opin Immunol. 1995;7(6):812-818. PubMed, CrossRef
  10. Panda S, Ding JK. Natural Antibodies Bridge Innate and Adaptive Immunity. J Immunol. 2015;194(1):13-20. PubMed, CrossRef
  11. Lopes-Carvalho T, Kearney JF. Development and Selection of Marginal Zone B Cells. Immunol Rev. 2004;197:192-205. PubMed, CrossRef
  12. Madi A, Hecht I, Bransburg-Zabary S, Merbl Y, Pick A, Zucker-Toledano M, Quintana FJ, Tauber AI, Cohen IR, Ben-Jacob E. 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(34):14484-14489.  PubMed, PubMedCentral, CrossRef
  13. Merbl Y, Zucker-Toledano M, Quintana FJ, Cohen IR. Newborn Humans Manifest Autoantibodies to Defined Self Molecules Detected by Antigen Microarray Informatics. J Clin Invest. 2007;117(3):712-718. PubMed, PubMedCentral, CrossRef
  14. Schettino EW, Chai SK, Kasaian MT, Schroeder HW Jr, Casali P. VHDJH Gene Sequences and Antigen Reactivity of Monoclonal Antibodies Produced by Human B-1 Cells: Evidence for Somatic Selection. J Immunol. 1997;158(5):2477-2489.  PubMed, PubMedCentral
  15. Jayasekera JP, Moseman EA, Carroll MC. Natural Antibody and Complement Mediate Neutralization of Influenza Virus in the Absence of Prior Immunity. J Virol. 2007;81(7):3487-3494. PubMed, PubMedCentral, CrossRef
  16. Nunes MC, Weinberg A, Cutland CL, Jones S, Wang D, Dighero-Kemp B, Levine MZ, Wairagkar N, Madhi SA. Neutralization and Hemagglutination-Inhibition Antibodies Following Influenza Vaccination of HIV-infected and HIV-uninfected Pregnant Woman. PLoS One. 2018;13(12):e0210124. PubMed, PubMedCentral, CrossRef
  17. Stegmann T, Bartoldus I, Zumbrunn J. Influenza Hemagglutinin-Mediated Membrane Fusion: Influence of Receptor Binding on the Lag Phase Preceding Fusion. Biochemistry. 1995;34(6):1825-1832. PubMed, CrossRef
  18. Beyer WEP, Palache AM, Lüchters G, Njauta J, Osterhaus ADME. Seroprotection Rate, Mean Fold Increase, Seroconversion Rate: Which Parameter Adequately Expresses Seroresponse to Influenza Vaccination? Virus Res. 2004;103(1-2):125-132. PubMed, CrossRef
  19. Laemmli UK. Cleavage of Structural Proteins During the Assembly of the Head of Bacteriophage T4. Nature. 1970;227(5259):680-685. PubMed, CrossRef
  20. Killian ML. Hemagglutination Assay for the Avian Influenza Virus. Methods Mol Biol. 2008;436:47-52. PubMed, CrossRef
  21. Baumgarth N. Innate-like B Cells and Their Rules of Engagement. Adv Exp Med Biol. 2013;785:57-66. PubMed, CrossRef
  22. Atif SM, Gibbings SL, Redente EF, Camp FA, Torres RM, Kedl RM, Henson PM, Jakubzick CV. Immune Surveillance by Natural IgM Is Required for Early Neoantigen Recognition and Initiation of Adaptive Immunity. Am J Respir Cell Mol Biol. 2018;59(5):580-591. PubMed, PubMedCentral, CrossRef
  23. Ehrenstein MR, Notley CA. The Importance of Natural IgM: Scavenger, Protector and Regulator. Nat Rev Immunol. 2010;10(11):778-786. PubMed, CrossRef
  24. Haury M, Sundblad A, Grandien A, Barreau C, Coutinho A, Nobrega A. The Repertoire of Serum IgM in Normal Mice Is Largely Independent of External Antigenic Contact. Eur J Immunol. 1997;27(6):1557-1563. PubMed, CrossRef
  25. Messmer BT, Sullivan JJ, Chiorazzi N, Rodman TC, Thaler DS. Two Human Neonatal IgM Antibodies Encoded by Different Variable-Region Genes Bind the Same Linear Peptide: Evidence for a Stereotyped Repertoire of Epitope Recognition. J Immunol. 1999;162(4):2184-2192. PubMed
  26. Heyman B, Shulman MJ. Structure, Function, and Production of Immunoglobulin M (IgM). Encyclopedia Immunobiol. 2016; 2: 1-14.  CrossRef
  27. Goudeau A, Yvonnet B, Lesage G, Barin F, Denis F, Coursaget P, Chiron JP, Mar ID. Lack of anti-HBc IgM in Neonates With HBsAg Carrier Mothers Argues Against Transplacental Transmission of Hepatitis B Virus Infection. Lancet. 1983;2(8359):1103-1104. PubMed, CrossRef
  28. Malek A, Sager R, Kuhn P, Nicolaides KH, Schneider H. Evolution of Maternofetal Transport of Immunoglobulins During Human Pregnancy. Am J Reprod Immunol. 1996;36(5):248-255. PubMed, CrossRef
  29. Petit T, Dommergues M, Socié G, Dumez Y, Gluckman E, Brison O. Detection of Maternal Cells in Human Fetal Blood During the Third Trimester of Pregnancy Using Allele-Specific PCR Amplification. Br J Haematol. 1997;98(3):767-771. PubMed, CrossRef
  30. Kanaan SB, Gammill HS, Harrington WE, De Rosa SC, Stevenson PA, Forsyth AM, Allen J, Cousin E, van Besien K, Delaney CS, Nelson JL. Maternal Microchimerism Is Prevalent in Cord Blood in Memory T Cells and Other Cell Subsets, and Persists Post-Transplant. Oncoimmunology. 2017;6(5):e1311436. PubMed, PubMedCentral, CrossRef
  31. Scaradavou A, Carrier C, Mollen N, Stevens C, Rubinstein P. Detection of Maternal DNA in placental/umbilical Cord Blood by Locus-Specific Amplification of the Noninherited Maternal HLA Gene. Blood. 1996;88(4):1494-1500. PubMed, CrossRef
  32. Ochsenbein AF, Fehr T, Lutz C, Suter M, Brombacher F, Hengartner H, Zinkernagel RM. Control of Early Viral and Bacterial Distribution and Disease by Natural Antibodies. Science. 1999;286(5447):2156-2159. PubMed, CrossRef
  33. Boes M, Prodeus AP, Schmidt T, Carroll MC, Chen J. A Critical Role of Natural Immunoglobulin M in Immediate Defense Against Systemic Bacterial Infection. J Exp Med. 1998;188(12):2381-2386. PubMed, PubMedCentral, CrossRef
  34. Harada Y, Muramatsu M, Shibata T, Honjo T, Kuroda K. Unmutated Immunoglobulin M Can Protect Mice From Death by Influenza Virus Infection. J Exp Med. 2003;197(12):1779-1785. PubMed, {pmc id=”PMC2193959″], CrossRef
  35. Racine R, Winslow GM. IgM in Microbial Infections: Taken for Granted? Immunol Lett. 2009;125(2):79-85. PubMed, PubMedCentral, CrossRef
  36. Karlsson F, Tremaroli V, Nielsen J, Bäckhed F. Assessing the Human Gut Microbiota in Metabolic Diseases. Diabetes. 2013;62(10):3341-3349. PubMed, PubMedCentral, CrossRef
  37. de Jong JC, Palache AM, Beyer WEP, Rimmelzwaan GF, Boon ACM, Osterhaus ADME. Haemagglutination-inhibiting Antibody to Influenza Virus. Dev Biol (Basel). 2003;115:63-73. PubMed
  38. Nikolayenko IV, Galkin OYu, Grabchenko NI, Spivak MYa. Preparation of highly purified human IgG, IgM, and IgA for immunization and immunoanalysis. Ukr Bioorg Acta. 2005; 2: 3-11.
  39. Baumgarth N, Herman OC, Jager GC, Brown LE, Herzenberg LA, Chen J. B-1 and B-2 Cell-Derived Immunoglobulin M Antibodies Are Nonredundant Components of the Protective Response to Influenza Virus Infection. J Exp Med. 2000;192(2):271-280. PubMed, PubMedCentral, CrossRef
  40. Wang H, Coligan JE, Morse HC 3rd. Emerging Functions of Natural IgM and Its Fc Receptor FCMR in Immune Homeostasis. Front Immunol. 2016;7:99.  PubMed, PubMedCentral, CrossRef
  41. Naparstek Y, André-Schwartz J, Manser T, Wysocki LJ, Breitman L, Stollar BD, Gefter M, Schwartz RS. A Single Germline VH Gene Segment of Normal A/J Mice Encodes Autoantibodies Characteristic of Systemic Lupus Erythematosus. J Exp Med. 1986;164(2):614-626. PubMed, PubMedCentral, CrossRef
  42. Avrameas S, Alexopoulos H, Moutsopoulos HM. Natural Autoantibodies: An Undersugn Hero of the Immune System and Autoimmune Disorders-A Point of View. Front Immunol. 2018;9:1320.  PubMed, PubMedCentral, CrossRef
  43. Haynes BF, Fleming J, St Clair EW , Katinger H, Stiegler G, Kunert R, James Robinson, Scearce RM, Plonk K, Staats HF, Ortel TL, Liao HX, Alam SM. Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies. Science. 2005;308(5730):1906-1908. PubMed, CrossRef
  44. Shaw PX, Goodyear CS, Chang MK, Witztum JL, Silverman GJ. The Autoreactivity of Anti-Phosphorylcholine Antibodies for Atherosclerosis-Associated Neo-Antigens and Apoptotic Cells. J Immunol. 2003;170(12):6151-6157. PubMed, CrossRef
  45. Palma J, Tokarz-Deptuła B, Deptuła J, Deptuła W. Natural Antibodies – Facts Known and Unknown. Cent Eur J Immunol. 2018;43(4):466-475. PubMed, PubMedCentral, CrossRef
  46. Rodriguez-Zhurbenko N, Quach TD, Hopkins TJ, Rothstein TL, Hernandez AM. Human B-1 Cells and B-1 Cell Antibodies Change With Advancing Age. Front Immunol. 2019;10:483. PubMed, PubMedCentral, CrossRef
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