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Clinical and Diagnostic Laboratory Immunology logoLink to Clinical and Diagnostic Laboratory Immunology
. 1994 Nov;1(6):640–644. doi: 10.1128/cdli.1.6.640-644.1994

Genetic diversity in human Fc receptor II for immunoglobulin G: Fc gamma receptor IIA ligand-binding polymorphism.

A F Reilly 1, C F Norris 1, S Surrey 1, F J Bruchak 1, E F Rappaport 1, E Schwartz 1, S E McKenzie 1
PMCID: PMC368380  PMID: 8556514

Abstract

Fc gamma receptors, and in particular genetic variation in these receptors, are important in disorders of hose defense, immunohematologic disease, and systemic autoimmune diseases. We investigated the His-Arg (CAT/CGT) polymorphism at codon 131 of the Fc gamma receptor IIA gene, which influences ligand binding by the receptor. Previously, individuals had been classified phenotypically on the basis of differential binding of murine immunoglobulin G1, but the Fc gamma receptor IIA genotype distribution has not been reported. We used selective PCR-based sequence analysis of genomic DNA to determine the distribution in healthy individuals. For African-Americans, the genotype distribution was determined to be A/A (14%), A/G (60%), and G/G (26%); for Caucasian Americans, the distribution was A/A (30%), A/G (51%), and G/G (19%). These data correlate well with phenotypic data. We implemented a nonradioactive single-stranded conformational polymorphism analysis to rapidly identify all three genotypes. The PCR-single-stranded conformational polymorphism analysis method will facilitate studies of the genotype distribution in individuals with disorders of immune function.

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  1. AboT, Tilden A. B., Balch C. M., Kumagai K., Troup G. M., Cooper M. D. Ethnic differences in the lymphocyte proliferative response induced by a murine IgG1 antibody, Leu-4, to the T3 molecule. J Exp Med. 1984 Jul 1;160(1):303–309. doi: 10.1084/jem.160.1.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Brooks D. G., Qiu W. Q., Luster A. D., Ravetch J. V. Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes. J Exp Med. 1989 Oct 1;170(4):1369–1385. doi: 10.1084/jem.170.4.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cartron J., Celton J. L., Gane P., Astier A., Fridman W. H., Boissinot G., Cartron J. P. Iso-immune neonatal neutropenia due to an anti-Fc receptor III (CD16) antibody. Eur J Pediatr. 1992 Jun;151(6):438–441. doi: 10.1007/BF01959359. [DOI] [PubMed] [Google Scholar]
  5. Cassel D. L., Keller M. A., Surrey S., Schwartz E., Schreiber A. D., Rappaport E. F., McKenzie S. E. Differential expression of Fc gamma RIIA, Fc gamma RIIB and Fc gamma RIIC in hematopoietic cells: analysis of transcripts. Mol Immunol. 1993 Apr;30(5):451–460. doi: 10.1016/0161-5890(93)90113-p. [DOI] [PubMed] [Google Scholar]
  6. Ceuppens J. L., Baroja M. L., Van Vaeck F., Anderson C. L. Defect in the membrane expression of high affinity 72-kD Fc gamma receptors on phagocytic cells in four healthy subjects. J Clin Invest. 1988 Aug;82(2):571–578. doi: 10.1172/JCI113634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Clark M. R., Liu L., Clarkson S. B., Ory P. A., Goldstein I. M. An abnormality of the gene that encodes neutrophil Fc receptor III in a patient with systemic lupus erythematosus. J Clin Invest. 1990 Jul;86(1):341–346. doi: 10.1172/JCI114706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. De Reys S., Blom C., Lepoudre B., Declerck P. J., De Ley M., Vermylen J., Deckmyn H. Human platelet aggregation by murine monoclonal antiplatelet antibodies is subtype-dependent. Blood. 1993 Apr 1;81(7):1792–1800. [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. Fromont P., Bettaieb A., Skouri H., Floch C., Poulet E., Duedari N., Bierling P. Frequency of the polymorphonuclear neutrophil Fc gamma receptor III deficiency in the French population and its involvement in the development of neonatal alloimmune neutropenia. Blood. 1992 Apr 15;79(8):2131–2134. [PubMed] [Google Scholar]
  13. 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]
  14. Hogarth P. M., Hulett M. D., Ierino F. L., Tate B., Powell M. S., Brinkworth R. I. Identification of the immunoglobulin binding regions (IBR) of Fc gamma RII and Fc epsilon RI. Immunol Rev. 1992 Feb;125:21–35. doi: 10.1111/j.1600-065x.1992.tb00623.x. [DOI] [PubMed] [Google Scholar]
  15. Hogarth P. M., Hulett M. D., Osman N. Fc gamma receptors: gene structure and receptor function. Immunol Res. 1992;11(3-4):217–225. doi: 10.1007/BF02919128. [DOI] [PubMed] [Google Scholar]
  16. Horsewood P., Hayward C. P., Warkentin T. E., Kelton J. G. Investigation of the mechanisms of monoclonal antibody-induced platelet activation. Blood. 1991 Aug 15;78(4):1019–1026. [PubMed] [Google Scholar]
  17. 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]
  18. Huizinga T. W., Roos D., von dem Borne A. E. Neutrophil Fc-gamma receptors: a two-way bridge in the immune system. Blood. 1990 Mar 15;75(6):1211–1214. [PubMed] [Google Scholar]
  19. McKenzie S. E., Schreiber A. D. Biological advances and clinical applications of Fc receptors for IgG. Curr Opin Hematol. 1994 Jan;1(1):45–52. [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Parren P. W., Warmerdam P. A., Boeije L. C., Capel P. J., van de Winkel J. G., Aarden L. A. Characterization of IgG FcR-mediated proliferation of human T cells induced by mouse and human anti-CD3 monoclonal antibodies. Identification of a functional polymorphism to human IgG2 anti-CD3. J Immunol. 1992 Feb 1;148(3):695–701. [PubMed] [Google Scholar]
  23. Qiu W. Q., de Bruin D., Brownstein B. H., Pearse R., Ravetch J. V. Organization of the human and mouse low-affinity Fc gamma R genes: duplication and recombination. Science. 1990 May 11;248(4956):732–735. doi: 10.1126/science.2139735. [DOI] [PubMed] [Google Scholar]
  24. Rappaport E. F., Cassel D. L., Walterhouse D. O., McKenzie S. E., Surrey S., Keller M. A., Schreiber A. D., Schwartz E. A soluble form of the human Fc receptor Fc gamma RIIA: cloning, transcript analysis and detection. Exp Hematol. 1993 May;21(5):689–696. [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. 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]
  28. Stuart S. G., Simister N. E., Clarkson S. B., Kacinski B. M., Shapiro M., Mellman I. Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium. EMBO J. 1989 Dec 1;8(12):3657–3666. doi: 10.1002/j.1460-2075.1989.tb08540.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sugano K., Kyogoku A., Fukayama N., Ohkura H., Shimosato Y., Sekiya T., Hayashi K. Methods in laboratory investigation. Rapid and simple detection of c-Ki-ras2 gene codon 12 mutations by nonradioisotopic single-strand conformation polymorphism analysis. Lab Invest. 1993 Mar;68(3):361–366. [PubMed] [Google Scholar]
  30. Tate B. J., Witort E., McKenzie I. F., Hogarth P. M. Expression of the high responder/non-responder human Fc gamma RII. Analysis by PCR and transfection into FcR-COS cells. Immunol Cell Biol. 1992 Apr;70(Pt 2):79–87. doi: 10.1038/icb.1992.12. [DOI] [PubMed] [Google Scholar]
  31. Tax W. J., Willems H. W., Reekers P. P., Capel P. J., Koene R. A. Polymorphism in mitogenic effect of IgG1 monoclonal antibodies against T3 antigen on human T cells. Nature. 1983 Aug 4;304(5925):445–447. doi: 10.1038/304445a0. [DOI] [PubMed] [Google Scholar]
  32. Tomiyama Y., Kunicki T. J., Zipf T. F., Ford S. B., Aster R. H. Response of human platelets to activating monoclonal antibodies: importance of Fc gamma RII (CD32) phenotype and level of expression. Blood. 1992 Nov 1;80(9):2261–2268. [PubMed] [Google Scholar]
  33. Unkeless J. C. Function and heterogeneity of human Fc receptors for immunoglobulin G. J Clin Invest. 1989 Feb;83(2):355–361. doi: 10.1172/JCI113891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. 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]
  37. 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]

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