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. 1995 Jan;63(1):73–81. doi: 10.1128/iai.63.1.73-81.1995

Human immunoglobulin G (IgG) Fc receptor IIA (CD32) polymorphism and IgG2-mediated bacterial phagocytosis by neutrophils.

L A Sanders 1, R G Feldman 1, M M Voorhorst-Ogink 1, M de Haas 1, G T Rijkers 1, P J Capel 1, B J Zegers 1, J G van de Winkel 1
PMCID: PMC172959  PMID: 7806386

Abstract

Human immunoglobulin G (IgG) Fc receptor IIa (Fc gamma RIIa; CD32) is expressed on phagocytes, triggers phagocytosis, and represents the sole Fc receptor for IgG (Fc gamma R) capable of interaction with IgG2, the main IgG subclass induced in response to bacterial capsular polysaccharides. The two genetically determined structurally different allotypes of human Fc gamma RIIa, the products of the Fc gamma RIIa-R131 and IIa-H131 alleles, have functionally different reactivities with human IgG2. In humans, the Fc gamma RIIa-H131 allotype is known to interact efficiently with complexed human IgG2, whereas the IIa-H131 allotype does so only poorly. This polymorphism may therefore have implications for IgG2-mediated phagocytosis of encapsulated bacteria and susceptibility to bacterial infections. Phagocytosis of IgG2-opsonized bacteria by homozygous Fc gamma RIIa-R/R131, heterozygous IIa-H/R131, and homozygous IIa-H/H131 polymorphonuclear cells (PMN) was compared. A higher phagocytic capacity of IgG2-opsonized group B type III streptococci by PMN of homozygous H/H131 individuals compared with PMN from homozygous R/R131 individuals was observed (P = 0.001), while heterozygous IIa-H/R131 PMN showed intermediate phagocytosis. In this model system, IgG2-mediated phagocytosis was independent of the Fc gamma RIIIb-NA1/NA2 allelic polymorphism.

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Selected References

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  1. Amir J., Scott M. G., Nahm M. H., Granoff D. M. Bactericidal and opsonic activity of IgG1 and IgG2 anticapsular antibodies to Haemophilus influenzae type b. J Infect Dis. 1990 Jul;162(1):163–171. doi: 10.1093/infdis/162.1.163. [DOI] [PubMed] [Google Scholar]
  2. Anderson C. L., Shen L., Eicher D. M., Wewers M. D., Gill J. K. Phagocytosis mediated by three distinct Fc gamma receptor classes on human leukocytes. J Exp Med. 1990 Apr 1;171(4):1333–1345. doi: 10.1084/jem.171.4.1333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bjerknes R., Bassøe C. F., Sjursen H., Laerum O. D., Solberg C. O. Flow cytometry for the study of phagocyte functions. Rev Infect Dis. 1989 Jan-Feb;11(1):16–33. doi: 10.1093/clinids/11.1.16. [DOI] [PubMed] [Google Scholar]
  4. Bredius R. G., de Vries C. E., Troelstra A., van Alphen L., Weening R. S., van de Winkel J. G., Out T. A. Phagocytosis of Staphylococcus aureus and Haemophilus influenzae type B opsonized with polyclonal human IgG1 and IgG2 antibodies. Functional hFc gamma RIIa polymorphism to IgG2. J Immunol. 1993 Aug 1;151(3):1463–1472. [PubMed] [Google Scholar]
  5. Clark M. R., Clarkson S. B., Ory P. A., Stollman N., Goldstein I. M. Molecular basis for a polymorphism involving Fc receptor II on human monocytes. J Immunol. 1989 Sep 1;143(5):1731–1734. [PubMed] [Google Scholar]
  6. Clark M. R., Stuart S. G., Kimberly R. P., Ory P. A., Goldstein I. M. A single amino acid distinguishes the high-responder from the low-responder form of Fc receptor II on human monocytes. Eur J Immunol. 1991 Aug;21(8):1911–1916. doi: 10.1002/eji.1830210820. [DOI] [PubMed] [Google Scholar]
  7. Emmrich F., Zenke G., Eichmann K. Isotype restriction of idiotopes associated with human anti-streptococcal A carbohydrate antibodies. Eur J Immunol. 1986 May;16(5):542–546. doi: 10.1002/eji.1830160514. [DOI] [PubMed] [Google Scholar]
  8. Feldman R. G., Ferrante A. Prevalence of anti-group B streptococcal type III capsular IgG antibodies in the United Kingdom and an analysis of their specific IgG subclasses. J Infect Dis. 1990 Oct;162(4):883–887. doi: 10.1093/infdis/162.4.883. [DOI] [PubMed] [Google Scholar]
  9. Feldman R. G., Hamel M. E., Breukels M. A., Concepcion N. F., Anthony B. F. Solid-phase antigen density and avidity of antibodies detected in anti-group B streptococcal type III IgG enzyme immunoassays. J Immunol Methods. 1994 Mar 29;170(1):37–45. doi: 10.1016/0022-1759(94)90243-7. [DOI] [PubMed] [Google Scholar]
  10. Ferrante A., Beard L. J., Feldman R. G. IgG subclass distribution of antibodies to bacterial and viral antigens. Pediatr Infect Dis J. 1990 Aug;9(8 Suppl):S16–S24. [PubMed] [Google Scholar]
  11. Fijen C. A., Bredius R. G., Kuijper E. J. Polymorphism of IgG Fc receptors in meningococcal disease. Ann Intern Med. 1993 Oct 1;119(7 Pt 1):636–636. doi: 10.7326/0003-4819-119-7_part_1-199310010-00026. [DOI] [PubMed] [Google Scholar]
  12. Fleit H. B., Wright S. D., Unkeless J. C. Human neutrophil Fc gamma receptor distribution and structure. Proc Natl Acad Sci U S A. 1982 May;79(10):3275–3279. doi: 10.1073/pnas.79.10.3275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Freijd A., Hammarström L., Persson M. A., Smith C. I. Plasma anti-pneumococcal antibody activity of the IgG class and subclasses in otitis prone children. Clin Exp Immunol. 1984 May;56(2):233–238. [PMC free article] [PubMed] [Google Scholar]
  14. Givner L. B., Baker C. J., Edwards M. S. Type III group B Streptococcus: functional interaction with IgG subclass antibodies. J Infect Dis. 1987 Mar;155(3):532–539. doi: 10.1093/infdis/155.3.532. [DOI] [PubMed] [Google Scholar]
  15. Gosselin E. J., Brown M. F., Anderson C. L., Zipf T. F., Guyre P. M. The monoclonal antibody 41H16 detects the Leu 4 responder form of human Fc gamma RII. J Immunol. 1990 Mar 1;144(5):1817–1822. [PubMed] [Google Scholar]
  16. Greenman J., Tutt A. L., George A. J., Pulford K. A., Stevenson G. T., Glennie M. J. Characterization of a new monoclonal anti-Fc gamma RII antibody, AT10, and its incorporation into a bispecific F(ab')2 derivative for recruitment of cytotoxic effectors. Mol Immunol. 1991 Nov;28(11):1243–1254. doi: 10.1016/0161-5890(91)90011-8. [DOI] [PubMed] [Google Scholar]
  17. Guyre P. M., Graziano R. F., Vance B. A., Morganelli P. M., Fanger M. W. Monoclonal antibodies that bind to distinct epitopes on Fc gamma RI are able to trigger receptor function. J Immunol. 1989 Sep 1;143(5):1650–1655. [PubMed] [Google Scholar]
  18. Hetherington S. V., Lepow M. L. Correlation between antibody affinity and serum bactericidal activity in infants. J Infect Dis. 1992 Apr;165(4):753–756. doi: 10.1093/infdis/165.4.753. [DOI] [PubMed] [Google Scholar]
  19. Huizinga T. W., Kuijpers R. W., Kleijer M., Schulpen T. W., Cuypers H. T., Roos D., von dem Borne A. E. Maternal genomic neutrophil FcRIII deficiency leading to neonatal isoimmune neutropenia. Blood. 1990 Nov 15;76(10):1927–1932. [PubMed] [Google Scholar]
  20. Huizinga T. W., de Haas M., Kleijer M., Nuijens J. H., Roos D., von dem Borne A. E. Soluble Fc gamma receptor III in human plasma originates from release by neutrophils. J Clin Invest. 1990 Aug;86(2):416–423. doi: 10.1172/JCI114727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Koenderman L., Hermans S. W., Capel P. J., van de Winkel J. G. Granulocyte-macrophage colony-stimulating factor induces sequential activation and deactivation of binding via a low-affinity IgG Fc receptor, hFc gamma RII, on human eosinophils. Blood. 1993 May 1;81(9):2413–2419. [PubMed] [Google Scholar]
  22. Looney R. J., Abraham G. N., Anderson C. L. Human monocytes and U937 cells bear two distinct Fc receptors for IgG. J Immunol. 1986 Mar 1;136(5):1641–1647. [PubMed] [Google Scholar]
  23. Lortan J. E., Kaniuk A. S., Monteil M. A. Relationship of in vitro phagocytosis of serotype 14 Streptococcus pneumoniae to specific class and IgG subclass antibody levels in healthy adults. Clin Exp Immunol. 1993 Jan;91(1):54–57. doi: 10.1111/j.1365-2249.1993.tb03353.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Michaelsen T. E., Garred P., Aase A. Human IgG subclass pattern of inducing complement-mediated cytolysis depends on antigen concentration and to a lesser extent on epitope patchiness, antibody affinity and complement concentration. Eur J Immunol. 1991 Jan;21(1):11–16. doi: 10.1002/eji.1830210103. [DOI] [PubMed] [Google Scholar]
  25. Naziruddin B., Duffy B. F., Tucker J., Mohanakumar T. Evidence for cross-regulation of Fc gamma RIIIB (CD16) receptor-mediated signaling by Fc gamma RII (CD32) expressed on polymorphonuclear neutrophils. J Immunol. 1992 Dec 1;149(11):3702–3709. [PubMed] [Google Scholar]
  26. Noya F. J., Baker C. J., Edwards M. S. Neutrophil Fc receptor participation in phagocytosis of type III group B streptococci. Infect Immun. 1993 Apr;61(4):1415–1420. doi: 10.1128/iai.61.4.1415-1420.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ory P. A., Clark M. R., Kwoh E. E., Clarkson S. B., Goldstein I. M. Sequences of complementary DNAs that encode the NA1 and NA2 forms of Fc receptor III on human neutrophils. J Clin Invest. 1989 Nov;84(5):1688–1691. doi: 10.1172/JCI114350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ory P. A., Goldstein I. M., Kwoh E. E., Clarkson S. B. Characterization of polymorphic forms of Fc receptor III on human neutrophils. J Clin Invest. 1989 May;83(5):1676–1681. doi: 10.1172/JCI114067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Parren P. W., Warmerdam P. A., Boeije L. C., Arts J., Westerdaal N. A., Vlug A., Capel P. J., Aarden L. A., van de Winkel J. G. On the interaction of IgG subclasses with the low affinity Fc gamma RIIa (CD32) on human monocytes, neutrophils, and platelets. Analysis of a functional polymorphism to human IgG2. J Clin Invest. 1992 Oct;90(4):1537–1546. doi: 10.1172/JCI116022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Persson M. A., Brown S. E., Steward M. W., Hammarström L., Smith C. I., Howard C. R., Wahl M., Rynnel-Dagö B., Lefranc G., Carbonara A. O. IgG subclass-associated affinity differences of specific antibodies in humans. J Immunol. 1988 Jun 1;140(11):3875–3879. [PubMed] [Google Scholar]
  31. Perussia B., Ravetch J. V. Fc gamma RIII (CD16) on human macrophages is a functional product of the Fc gamma RIII-2 gene. Eur J Immunol. 1991 Feb;21(2):425–429. doi: 10.1002/eji.1830210226. [DOI] [PubMed] [Google Scholar]
  32. Preud'homme J. L., Hanson L. A. IgG subclass deficiency. Immunodefic Rev. 1990;2(2):129–149. [PubMed] [Google Scholar]
  33. Ravetch J. V., Kinet J. P. Fc receptors. Annu Rev Immunol. 1991;9:457–492. doi: 10.1146/annurev.iy.09.040191.002325. [DOI] [PubMed] [Google Scholar]
  34. Sahlin S., Hed J., Rundquist I. Differentiation between attached and ingested immune complexes by a fluorescence quenching cytofluorometric assay. J Immunol Methods. 1983 May 27;60(1-2):115–124. doi: 10.1016/0022-1759(83)90340-x. [DOI] [PubMed] [Google Scholar]
  35. Salmon J. E., Brogle N. L., Edberg J. C., Kimberly R. P. Fc gamma receptor III induces actin polymerization in human neutrophils and primes phagocytosis mediated by Fc gamma receptor II. J Immunol. 1991 Feb 1;146(3):997–1004. [PubMed] [Google Scholar]
  36. Salmon J. E., Edberg J. C., Brogle N. L., Kimberly R. P. Allelic polymorphisms of human Fc gamma receptor IIA and Fc gamma receptor IIIB. Independent mechanisms for differences in human phagocyte function. J Clin Invest. 1992 Apr;89(4):1274–1281. doi: 10.1172/JCI115712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Salmon J. E., Edberg J. C., Kimberly R. P. Fc gamma receptor III on human neutrophils. Allelic variants have functionally distinct capacities. J Clin Invest. 1990 Apr;85(4):1287–1295. doi: 10.1172/JCI114566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Salmon J. E., Kapur S., Kimberly R. P. Opsonin-independent ligation of Fc gamma receptors. The 3G8-bearing receptors on neutrophils mediate the phagocytosis of concanavalin A-treated erythrocytes and nonopsonized Escherichia coli. J Exp Med. 1987 Dec 1;166(6):1798–1813. doi: 10.1084/jem.166.6.1798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sanders L. A., van de Winkel J. G., Rijkers G. T., Voorhorst-Ogink M. M., de Haas M., Capel P. J., Zegers B. J. Fc gamma receptor IIa (CD32) heterogeneity in patients with recurrent bacterial respiratory tract infections. J Infect Dis. 1994 Oct;170(4):854–861. doi: 10.1093/infdis/170.4.854. [DOI] [PubMed] [Google Scholar]
  40. Scott M. G., Briles D. E., Shackelford P. G., Smith D. S., Nahm M. H. Human antibodies to phosphocholine. IgG anti-PC antibodies express restricted numbers of V and C regions. J Immunol. 1987 May 15;138(10):3325–3331. [PubMed] [Google Scholar]
  41. Scott M. G., Tarrand J. J., Crimmins D. L., McCourt D. W., Siegel N. R., Smith C. E., Nahm M. H. Clonal characterization of the human IgG antibody repertoire to Haemophilus influenzae type b polysaccharide. II. IgG antibodies contain VH genes from a single VH family and VL genes from at least four VL families. J Immunol. 1989 Jul 1;143(1):293–298. [PubMed] [Google Scholar]
  42. Shackelford P. G., Nelson S. J., Palma A. T., Nahm M. H. Human antibodies to group A streptococcal carbohydrate. Ontogeny, subclass restriction, and clonal diversity. J Immunol. 1988 May 1;140(9):3200–3205. [PubMed] [Google Scholar]
  43. Todd R. F., 3rd, Nadler L. M., Schlossman S. F. Antigens on human monocytes identified by monoclonal antibodies. J Immunol. 1981 Apr;126(4):1435–1442. [PubMed] [Google Scholar]
  44. Warmerdam P. A., van de Winkel J. G., Gosselin E. J., Capel P. J. Molecular basis for a polymorphism of human Fc gamma receptor II (CD32). J Exp Med. 1990 Jul 1;172(1):19–25. doi: 10.1084/jem.172.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Warmerdam P. A., van de Winkel J. G., Vlug A., Westerdaal N. A., Capel P. J. A single amino acid in the second Ig-like domain of the human Fc gamma receptor II is critical for human IgG2 binding. J Immunol. 1991 Aug 15;147(4):1338–1343. [PubMed] [Google Scholar]
  46. Wee S. L., Colvin R. B., Phelan J. M., Preffer F. I., Reichert T. A., Berd D., Cosimi A. B. Fc-receptor for mouse IgG1 (Fc gamma RII) and antibody-mediated cell clearance in patients treated with Leu2a antibody. Transplantation. 1989 Dec;48(6):1012–1017. doi: 10.1097/00007890-198912000-00024. [DOI] [PubMed] [Google Scholar]
  47. White-Owen C., Alexander J. W., Sramkoski R. M., Babcock G. F. Rapid whole-blood microassay using flow cytometry for measuring neutrophil phagocytosis. J Clin Microbiol. 1992 Aug;30(8):2071–2076. doi: 10.1128/jcm.30.8.2071-2076.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. van de Winkel J. G., Capel P. J. Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications. Immunol Today. 1993 May;14(5):215–221. doi: 10.1016/0167-5699(93)90166-I. [DOI] [PubMed] [Google Scholar]
  49. van der Reijden H. J., van Rhenen D. J., Lansdorp P. M., van't Veer M. B., Langenhuijsen M. M., Engelfriet C. P., von dem Borne A. E. A comparison of surface marker analysis and FAB classification in acute myeloid leukemia. Blood. 1983 Mar;61(3):443–448. [PubMed] [Google Scholar]

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