Skip to main content

Nature and Nurture of Catalytic Antibodies

  • Chapter
Naturally Occurring Antibodies (NAbs)

Abstract

Immunoglobulins (antibodies) frequently express constitutive functions. Two such functions are nucleophilic catalysis and the reversible binding to B-cell superantigens. Constitutive or “naturally-occurring” antibodies are produced spontaneously from germline genetic information. The antibody structural elements mediating the constitutive functions have originated over millions of years of phylogenic evolution, contrasting with antigen-driven, somatic sequence diversification of the complementarity determining regions (CDR) that underlies the better-known high affinity antigen binding function of antibodies. Often, the framework regions (FRs) play a dominant role in antibody constitutive functions. Catalytic antibody subsets with promiscuous, autoantigen-directed and microbe-directed specificities have been identified. Mucosal antibodies may be specialized to express high-level catalytic activity against microbes transmitted by the mucosal route, exemplified by constitutive production of IgA class antibodies in mucosal secretions that catalyze the cleavage of HIV gp120. Catalytic specificity can be gained by constitutive noncovalent superantigen binding at the FRs and by adaptive development of noncovalent classical antigen or superantigen binding, respectively, at the CDRs and FRs. Growing evidence suggests important functional roles for catalytic antibodies in homeostasis, autoimmune disease and protection against infection. Adaptive antibody responses to microbial superantigens are proscribed underphysiological circumstances. Covalent electrophilic immunogen binding to constitutively expressed nucleophilic sites in B-cell receptors bypasses the restriction on adaptive antibody production, and simultaneous occupancy of the CDR binding site by a stimulatory antigenic epitope can also overcome the downregulatory effect of superantigen binding at the FRs. These concepts may be useful for developing novel vaccines that capitalize and improve on constitutive antibody functions for protection against microbes.

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

Access this chapter

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. Dooley H, Flajnik MF. Antibody repertoire development in cartilaginous fish. Dev Comp Immunol 2006; 30:43–56; PMID: 16146649; http://dx.doi.org/10.1016/j.dci.2005.06.022.

    Article  PubMed  CAS  Google Scholar 

  2. Schluter SF, Bernstein RM, Bernstein H et al. ‘Big Bang’ emergence of the combinatorial immune system. Dev Comp Immunol 1999; 23:107–11; PMID: 10227478.

    Article  PubMed  CAS  Google Scholar 

  3. Casali P, Schettino EW. Structure and function of natural antibodies. Curr Top Microbiol Immunol 1996; 210:167–79; PMID:8565555.

    Article  PubMed  CAS  Google Scholar 

  4. Guilbert B, Dighiero G, Avrameas S. Naturally occurring antibodies against nine common antigens in human sera. I. Detection, isolation and characterization. J Immunol 1982; 128:2779–87; PMID:6176652.

    PubMed  CAS  Google Scholar 

  5. Barbouche R, Forveille M, Fischer A et al. Spontaneous IgM autoantibody production in vitro by B lymphocytes of normal human neonates. Scand J Immunol 1992; 35:659–67; PMID: 1376488; http://dx.doi.org/10.1111/j.1365-3083.1992.tb02972.x.

    Article  PubMed  CAS  Google Scholar 

  6. Köhler F, Hug E, Eschbach C et al. Autoreactive B cell receptors mimic autonomous pre-B cell receptor signaling and induce proliferation of early B cells. Immunity 2008; 29:912–21; PMID: 19084434; http://dx.doi.org/10.1016/j.immuni.2008.10.013.

    Article  PubMed  Google Scholar 

  7. Tramontano A, Janda KD, Lerner RA. Catalytic antibodies. Science 1986; 234:1566–70; PMID:3787261; http://dx.doi.org/10.1126/science.3787261.

    Article  PubMed  CAS  Google Scholar 

  8. Paul S, Volle DJ, Beach CM et al. Catalytic hydrolysis of vasoactive intestinal peptide by human autoantibody. Science 1989; 244:1158–62; PMID:2727702; http://dx.doi.org/10.1126/science.2727702.

    Article  PubMed  CAS  Google Scholar 

  9. Shuster AM, Gololobov GV, Kvashuk OA et al. DNA hydrolyzing autoantibodies. Science 1992; 256:665–7; PMID:1585181; http://dx.doi.org/10.1126/science.1585181.

    Article  PubMed  CAS  Google Scholar 

  10. Zhou GW, Guo J, Huang W et al. Crystal structure of a catalytic antibody with a serine protease active site. Science 1994; 265:1059–64; PMID:8066444; http://dx.doi.org/10.1126/science.8066444.

    Article  PubMed  CAS  Google Scholar 

  11. Nishiyama Y, Taguchi H, Luo JQ et al. Covalent reactivity of phosphonate monophenyl esters with serine proteinases: an overlooked feature of presumed transition state analogs. Arch Biochem Biophys 2002; 402:281–8; PMID:12051675; http://dx.doi.org/10.1016/S0003-9861(02)00087-5.

    Article  PubMed  CAS  Google Scholar 

  12. Avalle B, Thomas D, Friboulet A. Functional mimicry: elicitation of a monoclonal anti-idiotypic antibody hydrolizing beta-lactams. FASEB J 1998; 12:1055–60; PMID:9707178.

    PubMed  CAS  Google Scholar 

  13. Kohler H, Paul S. Superantibody activities: new players in innate and adaptive immune responses. Immunol Today 1998; 19:221–7; PMID:9613040; http://dx.doi.org/10.1016/S0167-5699(97)01234-6.

    Article  PubMed  CAS  Google Scholar 

  14. Paul S, Planque S, Zhou YX et al. Specific HIV gp120-cleaving antibodies induced by covalently reactive analog of gp120. J Biol Chem 2003; 278:20429–35; PMID:12665517; http://dx.doi.org/10.1074/jbc.M300870200.

    Article  PubMed  CAS  Google Scholar 

  15. Gao QS, Sun M, Rees AR et al. Site-directed mutagenesis of proteolytic antibody light chain. J Mol Biol 1995; 253:658–64; PMID:7473741; http://dx.doi.org/10.1006/jmbi.1995.0580.

    Article  PubMed  CAS  Google Scholar 

  16. Gololobov G, Sun M, Paul S. Innate antibody catalysis. Mol Immunol 1999; 36:1215–22; PMID: 10684961; http://dx.doi.org/10.1016/S0161-5890(99)00141-8.

    Article  PubMed  CAS  Google Scholar 

  17. Sharma V, Heriot W, Trisler K et al. A human germ line antibody light chain with hydrolytic properties associated with multimerization status. J Biol Chem 2009; 284:33079–87; PMID: 19801545; http://dx.doi.org/10.1074/jbc.M109.036087.

    Article  PubMed  CAS  Google Scholar 

  18. Kalaga R, Li L, O’Dell JR et al. Unexpected presence of polyreactive catalytic antibodies in IgG from unimmunized donors and decreased levels in rheumatoid arthritis. J Immunol 1995; 155:2695–702; PMID:7650397.

    PubMed  CAS  Google Scholar 

  19. Planque S, Bangale Y, Song XT et al. Ontogeny of proteolytic immunity: IgM serine proteases. J Biol Chem 2004; 279:14024–32; PMID:14726510; http://dx.doi.org/10.1074/jbc.M312152200.

    Article  PubMed  CAS  Google Scholar 

  20. Lacroix-Desmazes S, Bayry J, Kaveri SV et al. High levels of catalytic antibodies correlate with favorable outcome in sepsis. Proc Natl Acad Sci USA 2005; 102:4109–13; PMID:15743915; http://dx.doi.org/10.1073/pnas.0500586102.

    Article  PubMed  CAS  Google Scholar 

  21. Taguchi H, Planque S, Sapparapu G et al. Exceptional amyloid beta peptide hydrolyzing activity of nonphysiological immunoglobulin variable domain scaffolds. J Biol Chem 2008; 283:36724–33; PMID: 18974093; http://dx.doi.org/10.1074/jbc.M806766200.

    Article  PubMed  CAS  Google Scholar 

  22. Mitsuda Y, Planque S, Hara M et al. Naturally occurring catalytic antibodies: evidence for preferred development of the catalytic function in IgA class antibodies. Mol Biotechnol 2007; 36:113–22; PMID: 17914190; http://dx.doi.org/10.1007/s12033-007-0003-7.

    Article  PubMed  CAS  Google Scholar 

  23. Sun M, Li L, Gao QS et al. Antigen recognition by an antibody light chain. J Biol Chem 1994; 269:734–8; PMID: 8276876.

    PubMed  CAS  Google Scholar 

  24. Matsuura K, Yamamoto K, Sinohara H. Amidase activity of human Bence Jones proteins. Biochem Biophys Res Commun 1994; 204:57–62; PMID:7945392; http://dx.doi.org/10.1006/bbrc.1994.2425.

    Article  PubMed  CAS  Google Scholar 

  25. Paul S, Li L, Kalaga R et al. Natural catalytic antibodies: peptide-hydrolyzing activities of Bence Jones proteins and VL fragment. J Biol Chem 1995; 270:15257–61; PMID:7797511; http://dx.doi.org/10.1074/jbc.270.25.15257.

    Article  PubMed  CAS  Google Scholar 

  26. Matsuura K, Ohara K, Munakata H et al. Pathogenicity of catalytic antibodies: catalytic activity of Bence Jones proteins from myeloma patients with renal impairment can elicit cytotoxic effects. Biol Chem 2006; 387:543–8; PMID:16740125; http://dx.doi.org/10.1515/BC.2006.070.

    Article  PubMed  CAS  Google Scholar 

  27. Buneva VN, Kanyshkova TG, Vlassov AV et al. Catalytic DNA-and RNA-hydrolyzing antibodies from milk of healthy human mothers. Appl Biochem Biotechnol 1998; 75:63–76; PMID:10214697; http://dx.doi.org/10.1007/BF02787709.

    Article  PubMed  CAS  Google Scholar 

  28. Li L, Paul S, Tyutyulkova S et al. Catalytic activity of anti-thyroglobulin antibodies. J Immunol 1995; 154:3328–32; PMID:7897215.

    PubMed  CAS  Google Scholar 

  29. Thiagarajan P, Dannenbring R, Matsuura K et al. Monoclonal antibody light chain with prothrombinase activity. Biochemistry 2000; 39:6459–65; PMID: 10828960; http://dx.doi.org/10.1021/bi992588w.

    Article  PubMed  CAS  Google Scholar 

  30. Yang YH, Chang CJ, Chuang YH et al. Identification of anti-prothrombin antibodies in the anti-phospholipid syndrome that display the prothrombinase activity. Rheumatology (Oxford) 2010; 49:34–42; PMID: 19920091; http://dx.doi.org/10.1093/rheumatology/kep328.

    Article  Google Scholar 

  31. Wootla B, Dasgupta S, Dimitrov JD et al. Factor VIII hydrolysis mediated by anti-factor VIII autoantibodies in acquired hemophilia. J Immunol 2008; 180:7714–20; PMID: 18490775.

    PubMed  CAS  Google Scholar 

  32. Wootla B, Christophe OD, Mahendra A et al. Proteolytic antibodies activate factor IX in patients with acquired hemophilia. Blood 2011; 117:2257–64; PMID:21131590; http://dx.doi.org/10.1182/blood-2010-07-296103.

    Article  PubMed  CAS  Google Scholar 

  33. Ponomarenko NA, Durova OM, Vorobiev II et al. Autoantibodies to myelinbasic protein catalyze site-specific degradation of their antigen. Proc Natl Acad Sci USA 2006; 103:281–6; PMID:16387849; http://dx.doi.org/10.1073/pnas.0509849103.

    Article  PubMed  CAS  Google Scholar 

  34. Taguchi H, Planque S, Nishiyama Y et al. Autoantibody-catalyzed hydrolysis of amyloid beta peptide. J Biol Chem 2008; 283:4714–22; PMID: 18086674; http://dx.doi.org/10.1074/jbc.M707983200.

    Article  PubMed  CAS  Google Scholar 

  35. Sun M, Gao QS, Kirnarskiy L et al. Cleavage specificity of a proteolytic antibody light chain and effects of the heavy chain variable domain. J Mol Biol 1997; 271:374–85; PMID:9268666; http://dx.doi.org/10.1006/jmbi.1997.1196.

    Article  PubMed  CAS  Google Scholar 

  36. Lacroix-Desmazes S, Moreau A, Sooryanarayana et al. Catalytic activity of antibodies against factor VIII in patients with hemophilia. Nat Med 1999; 5:1044–7; PMID: 10470082; http://dx.doi.org/10.1038/12483.

    Article  PubMed  CAS  Google Scholar 

  37. Ames PR, Alves J, Murat I et al. Oxidative stress in systemic lupus erythematosus and allied conditions with vascular involvement. Rheumatology (Oxford) 1999; 38:529–34; PMID: 10402073; http://dx.doi.org/10.1093/rheumatology/38.6.529.

    Article  CAS  Google Scholar 

  38. Nevinsky GA, Buneva VN. Catalytic antibodies in healthy humans and patients with autoimmune and viral diseases. J Cell Mol Med 2003; 7:265–76; PMID: 14594551; http://dx.doi.org/10.1111/j.1582-4934.2003.tb00227.x.

    Article  PubMed  CAS  Google Scholar 

  39. Barrera GJ, Portillo R, Mijares A et al. Immunoglobulin A with protease activity secreted in human milk activates PAR-2 receptors, of intestinal epithelial cells HT-29, and promotes beta-defensin-2 expression. Immunol Lett 2009; 123:52–9; PMID: 19428552; http://dx.doi.org/10.1016/j.imlet.2009.02.001.

    Article  PubMed  CAS  Google Scholar 

  40. Graille M, Stura EA, Corper AL et al. Crystal structure of a Staphylococcus aureus protein A domain complexed with the Fab fragment of a human IgM antibody: structural basis for recognition of B-cell receptors and superantigen activity. Proc Natl Acad Sci USA 2000; 97:5399–404; PMID: 10805799; http://dx.doi.org/10.1073/pnas.97.10.5399.

    Article  PubMed  CAS  Google Scholar 

  41. Neshat MN, Goodglick L, Lim K et al. Mapping the B cell superantigen binding site for HIV-1 gp120 on a V(H)3 Ig. Int Immunol 2000; 12:305–12; PMID: 10700465; http://dx.doi.org/10.1093/intimm/12.3.305.

    Article  PubMed  CAS  Google Scholar 

  42. Graille M, Stura EA, Housden NG et al. Complex between Peptostreptococcus magnus protein L and a human antibody reveals structural convergence in the interaction modes of Fab binding proteins. Structure 2001; 9:679–87; PMID:11587642; http://dx.doi.org/10.1016/S0969-2126(01)00630-X.

    Article  PubMed  CAS  Google Scholar 

  43. Goodglick L, Zevit N, Neshat MS et al. Mapping the Ig superantigen-binding site of HIV-1 gp120. J Immunol 1995; 155:5151–9; PMID:7594524.

    PubMed  CAS  Google Scholar 

  44. Karray S, Zouali M. Identification of the B cell superantigen-binding site of HIV-1 gp120. Proc Natl Acad Sci USA 1997; 94:1356–60; PMID:9037057; http://dx.doi.org/10.1073/pnas.94.4.1356.

    Article  PubMed  CAS  Google Scholar 

  45. Planque S, Nishiyama Y, Taguchi H et al. Catalytic antibodies to HIV: physiological role andpotential clinical utility. Autoimmun Rev 2008; 7:473–9; PMID:18558365; http://dx.doi.org/10.1016/j.autrev.2008.04.002.

    Article  PubMed  CAS  Google Scholar 

  46. Paul S, Karle S, Planque S et al. Naturally occurring proteolytic antibodies: selective immunoglobulin M-catalyzed hydrolysis of HIV gp120. J Biol Chem 2004; 279:39611–9; PMID: 15269209; http://dx.doi.org/10.1074/jbc.M406719200.

    Article  PubMed  CAS  Google Scholar 

  47. Planque S, Mitsuda Y, Taguchi H et al. Characterization of gp120 Hydrolysis by IgA Antibodies from Humans without HIV Infection. AIDS Res Hum Retroviruses 2007; 23:1541–54; PMID: 18160012; http://dx.doi.org/10.1089/aid.2007.0081.

    Article  PubMed  CAS  Google Scholar 

  48. Bermas BL, Petri M, Berzofsky JA et al. Binding of glycoprotein 120 and peptides from the HIV-1 envelope by autoantibodies in mice with experimentally induced systemic lupus erythematosus and in patients with the disease. AIDS Res Hum Retroviruses 1994; 10:1071–7; PMID:7826694; http://dx.doi.org/10.1089/aid.1994.10.1071.

    Article  PubMed  CAS  Google Scholar 

  49. Daikh BE, Holyst MM. Lupus-specific autoantibodies in concomitant human immunodeficiency virus and systemic lupus erythematosus: case report and literature review. Semin Arthritis Rheum 2001; 30:418–25; PMID: 11404825; http://dx.doi.org/10.1053/sarh.2001.23149.

    Article  PubMed  CAS  Google Scholar 

  50. Paul S, Li L, Kalaga R et al. Characterization of thyroglobulin-directed andpolyreactive catalytic antibodies in autoimmune disease. J Immunol 1997; 159:1530–6; PMID:9233652.

    PubMed  CAS  Google Scholar 

  51. Nishiyama Y, Karle S, Planque S et al. Antibodies to the superantigenic site of HIV-1 gp120: hydrolytic and binding activities of the light chain subunit. Mol Immunol 2007; 44:2707–18; PMID: 17222909; http://dx.doi.org/10.1016/j.molimm.2006.12.005.

    Article  PubMed  CAS  Google Scholar 

  52. Urnovitz HB, Murphy WH. Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease. Clin Microbiol Rev 1996; 9:72–99; PMID:8665478.

    PubMed  CAS  Google Scholar 

  53. Planque S, Salas M, Mitsuda Y et al. Neutralization of genetically diverse HIV-1 strains by IgA antibodies to the gp120-CD4-binding site from long-term survivors of HIV infection. AIDS 2010; 24:875–84; PMID:20186035; http://dx.doi.org/10.1097/QAD.0b013e3283376e88.

    Article  PubMed  CAS  Google Scholar 

  54. Odintsova ES, Kharitonova MA, Baranovskii AG et al. Proteolytic activity of IgG antibodies from blood of acquired immunodeficiency syndrome patients. Biochemistry (Mosc) 2006; 71:251–61; PMID: 16545061; http://dx.doi.org/10.1134/S0006297906030047.

    Article  CAS  Google Scholar 

  55. Baranova SV, Buneva VN, Kharitonova MA et al. HIV-1 integrase-hydrolyzing IgM antibodies from sera of HIV-infected patients. Int Immunol 2010; 22:671–80; PMID:20507874; http://dx.doi.org/10.1093/intimm/dxq051.

    Article  PubMed  CAS  Google Scholar 

  56. Brody DL, Holtzman DM. Active and passive immunotherapy for neurodegenerative disorders. Annu Rev Neurosci 2008; 31:175–93; PMID:18352830; http://dx.doi.org/10.1146/annurev.neuro.31.060407.125529.

    Article  PubMed  CAS  Google Scholar 

  57. Salloway S, Sperling R, Gilman S et al. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology 2009; 73:2061–70; PMID:19923550; http://dx.doi.org/10.1212/WNL.0b013e3181c67808.

    Article  PubMed  CAS  Google Scholar 

  58. Kasturirangan S, Boddapati S, Sierks MR. Engineered proteolytic nanobodies reduce Abeta burden and ameliorate Abeta-induced cytotoxicity. Biochemistry 2010; 49:4501–8; PMID:20429609; http://dx.doi.org/10.1021/bi902030m.

    Article  PubMed  CAS  Google Scholar 

  59. Hifumi E, Morihara F, Hatiuchi K et al. Catalytic features and eradication ability of antibody light-chain UA15-L against Helicobacter pylori. J Biol Chem 2008; 283:899–907; PMID: 17991752; http://dx.doi.org/10.1074/jbc.M705674200.

    Article  PubMed  CAS  Google Scholar 

  60. Nishiyama Y, Planque S, Mitsuda Y et al. Toward effective HIV vaccination: induction of binary epitope reactive antibodies withbroad HIV neutralizing activity. J Biol Chem 2009; 284:30627–42; PMID:19726674; http://dx.doi.org/10.1074/jbc.M109.032185.

    Article  PubMed  CAS  Google Scholar 

  61. Planque S, Mitsuda Y, Ghosh D et al. Prototype covalent HIV vaccine for inducing antibodies that neutralize genetically divergent virus strains. XVIII International AIDS Conference (AIDS 2010) 2010; Abstract: TUAA0101. http://pag.aids2010.org/flash/?pid=100572.

  62. Vercruysse T, Pardon E, Vanstreels E et al. An intrabody based on a llama single-domain antibody targeting the N-terminal alpha-helical multimerization domain of HIV-1 rev prevents viral production. J Biol Chem 2010; 285:21768–80; PMID:20406803; http://dx.doi.org/10.1074/jbc.M110.112490.

    Article  PubMed  CAS  Google Scholar 

  63. Savarino A, Mai A, Norelli S et al. “Shock and kill” effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescence. Retrovirology 2009; 6:52; PMID:19486542; http://dx.doi.org/10.1186/1742-4690-6-52.

    Article  PubMed  Google Scholar 

  64. Planque S, Taguchi H, Burr G et al. Broadly distributed chemical reactivity of natural antibodies expressed in coordination with specific antigen binding activity. J Biol Chem 2003; 278:20436–43; PMID: 12668670; http://dx.doi.org/10.1074/jbc.M301468200.

    Article  PubMed  CAS  Google Scholar 

  65. Nishiyama Y, Mitsuda Y, Taguchi H et al. Towards covalent vaccination: improved polyclonal HIV neutralizing antibody response induced by an electrophilic gp120 V3 peptide analog. J Biol Chem 2007; 282:31250–6; PMID: 17728243; http://dx.doi.org/10.1074/jbc.M706471200.

    Article  PubMed  CAS  Google Scholar 

  66. Durova OM, Vorobiev II, Smirnov IV et al. Strategies for induction of catalytic antibodies toward HIV-1 glycoprotein gp120 in autoimmune prone mice. Mol Immunol 2009; 47:87–95; PMID: 19201029; http://dx.doi.org/10.1016/j.molimm.2008.12.020.

    Article  PubMed  CAS  Google Scholar 

  67. Paul S, Sun M, Mody R et al. Peptidolytic monoclonal antibody elicited by a neuropeptide. J Biol Chem 1992; 267:13142–5; PMID: 1377678.

    PubMed  CAS  Google Scholar 

  68. Mirshahi M, Shamsipour F, Mirshahi T et al. A novel monoclonal antibody with catalytic activity against beta human chorionic gonadotropin. Immunol Lett 2006; 106:57–62; PMID:16759712; http://dx.doi.org/10.1016/j.imlet.2006.04.008.

    Article  PubMed  CAS  Google Scholar 

  69. Nishiyama Y, Karle S, Mitsuda Y et al. Towards irreversible HIV inactivation: stable gp120 binding by nucleophilic antibodies. J Mol Recognit 2006; 19:423–31; PMID:16838382; http://dx.doi.org/10.1002/jmr.795.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sudhir Paul .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Paul, S., Planque, S.A., Nishiyama, Y., Hanson, C.V., Massey, R.J. (2012). Nature and Nurture of Catalytic Antibodies. 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_5

Download citation

Publish with us

Policies and ethics