Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Apr 1990; 85(4): 1287–1295.
PMCID: PMC296565

Fc gamma receptor III on human neutrophils. Allelic variants have functionally distinct capacities.


As a model system to explore the functional consequences of structural variants of human Fc gamma receptors (Fc gamma R), we have investigated Fc gamma R-mediated phagocytosis in relation to the NA1-NA2 polymorphism of Fc gamma RIII (CD16) on neutrophils (Fc gamma RIIIPMN). The neutrophil-specific NA antigen system is a biallelic polymorphism with codominant expression demonstrating a gene dose effect with the anti-NA1 MAb CLB-gran 11 in a large donor population. To explore the impact of this allelic variation of Fc gamma RIIIPMN on phagocytosis, we used two Fc gamma RIII-dependent probes, IgG-sensitized erythrocytes (EA) and concanavalin. A-treated erythrocytes (E-ConA). Comparison of Fc gamma R-mediated phagocytosis by PMN from NA1 subjects and from NA2 subjects showed lower levels of phagocytosis of both probes by the NA2 individuals. The difference was most pronounced with lightly opsonized EA: at the lowest level of sensitization the phagocytic index was 72% lower for NA2 donors, whereas at the highest level of sensitization it was 21% lower (P less than 0.003). Blockade of Fc gamma RII with MAb IV.3 Fab amplified by threefold the difference between NA1 and NA2 donors. NA1 and NA2 individuals had identical phagocytic capacities for the non-Fc gamma RIII probes, serum-treated and heat-treated zymosan. These individuals did not show differential quantitative cell surface expression of Fc gamma RIIIPMN measured by a panel of anti-CD16 MAb (3G8, CLB FcR-gran 1, VEP13, BW209/2) and by Scatchard analysis of 125I-IgG dimer binding. The difference in Fc gamma R-mediated phagocytosis was not explicable on the basis of differential collaboration of Fc gamma RIIIPMN alleles with Fc gamma RII, since (a) the difference in phagocytic capacity between NA1 and NA2 individuals was readily apparent with the E-ConA probe (which is independent of Fc gamma RII) and (b) the difference in phagocytosis of EA was magnified by Fc gamma RII blockade. The demonstration that allelic polymorphisms in Fc gamma R can have significant consequences for physiological functions implies that within the structural complexity of human Fc gamma Rs, including both allelic forms and cell type-specific isoforms, there will be differences in quantitative, and perhaps qualitative, function with potential importance for disease processes.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Salmon JE, Kapur S, Kimberly RP. 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. [PMC free article] [PubMed]
  • Unkeless JC, Scigliano E, Freedman VH. Structure and function of human and murine receptors for IgG. Annu Rev Immunol. 1988;6:251–281. [PubMed]
  • Anderson CL, Ryan DH, Looney RJ, Leary PC. Structural polymorphism of the human monocyte 40 kilodalton Fc receptor for IgG. J Immunol. 1987 Apr 1;138(7):2254–2256. [PubMed]
  • Looney RJ, Anderson CL, Ryan DH, Rosenfeld SI. Structural polymorphism of the human platelet Fc gamma receptor. J Immunol. 1988 Oct 15;141(8):2680–2683. [PubMed]
  • Tax WJ, Hermes FF, Willems RW, Capel PJ, Koene RA. Fc receptors for mouse IgG1 on human monocytes: polymorphism and role in antibody-induced T cell proliferation. J Immunol. 1984 Sep;133(3):1185–1189. [PubMed]
  • AboT, Tilden AB, Balch CM, Kumagai K, Troup GM, Cooper MD. 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. [PMC free article] [PubMed]
  • Ceuppens JL, Bloemmen FJ, Van Wauwe JP. T cell unresponsiveness to the mitogenic activity of OKT3 antibody results from a deficiency of monocyte Fc gamma receptors for murine IgG2a and inability to cross-link the T3-Ti complex. J Immunol. 1985 Dec;135(6):3882–3886. [PubMed]
  • Lalezari P, Radel E. Neutrophil-specific antigens: immunology and clinical significance. Semin Hematol. 1974 Jul;11(3):281–290. [PubMed]
  • Ory PA, Clark MR, Kwoh EE, Clarkson SB, Goldstein IM. 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. [PMC free article] [PubMed]
  • Ravetch JV, Perussia B. Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions. J Exp Med. 1989 Aug 1;170(2):481–497. [PMC free article] [PubMed]
  • Kimberly RP, Gibofsky A, Salmon JE, Fotino M. Impaired fc-mediated mononuclear phagocyte system clearance in HLA-DR2 and MT1-positive healthy young adults. J Exp Med. 1983 May 1;157(5):1698–1703. [PMC free article] [PubMed]
  • Salmon JE, Kimberly RP, Gibofsky A, Fotino M. Defective mononuclear phagocyte function in systemic lupus erythematosus: dissociation of Fc receptor-ligand binding and internalization. J Immunol. 1984 Nov;133(5):2525–2531. [PubMed]
  • Salmon JE, Kimberly RP, Gibofsky A, Fotino M. Altered phagocytosis by monocytes from HLA-DR2 and DR3-positive healthy adults is Fc gamma receptor specific. J Immunol. 1986 May 15;136(10):3625–3630. [PubMed]
  • Shen L, Guyre PM, Anderson CL, Fanger MW. Heteroantibody-mediated cytotoxicity: antibody to the high affinity Fc receptor for IgG mediates cytotoxicity by human monocytes that is enhanced by interferon-gamma and is not blocked by human IgG. J Immunol. 1986 Dec 1;137(11):3378–3382. [PubMed]
  • Shen L, Guyre PM, Fanger MW. Polymorphonuclear leukocyte function triggered through the high affinity Fc receptor for monomeric IgG. J Immunol. 1987 Jul 15;139(2):534–538. [PubMed]
  • Graziano RF, Fanger MW. Fc gamma RI and Fc gamma RII on monocytes and granulocytes are cytotoxic trigger molecules for tumor cells. J Immunol. 1987 Nov 15;139(10):3536–3541. [PubMed]
  • Graziano RF, Looney RJ, Shen L, Fanger MW. Fc gamma R-mediated killing by eosinophils. J Immunol. 1989 Jan 1;142(1):230–235. [PubMed]
  • Lanier LL, Ruitenberg JJ, Phillips JH. Functional and biochemical analysis of CD16 antigen on natural killer cells and granulocytes. J Immunol. 1988 Nov 15;141(10):3478–3485. [PubMed]
  • Looney RJ, Ryan DH, Takahashi K, Fleit HB, Cohen HJ, Abraham GN, Anderson CL. Identification of a second class of IgG Fc receptors on human neutrophils. A 40 kilodalton molecule also found on eosinophils. J Exp Med. 1986 Apr 1;163(4):826–836. [PMC free article] [PubMed]
  • Antoun GR, Longenecker BM, Zipf TF. Comparison of the 40 kDa hematopoietic cell antigens bound by monoclonal antibodies IV.3, 41H.16 and KB61. Mol Immunol. 1989 Mar;26(3):333–338. [PubMed]
  • Goldman R, Cooper RA. Concanavalin A mediated attachment and ingestion of red blood cells by macrophages. Exp Cell Res. 1975 Oct 1;95(1):223–231. [PubMed]
  • Salmon JE, Kimberly RP. Phagocytosis of concanavalin A-treated erythrocytes is mediated by the Fc gamma receptor. J Immunol. 1986 Jul 15;137(2):456–462. [PubMed]
  • Kurlander RJ, Batker J. The binding of human immunoglobulin G1 monomer and small, covalently cross-linked polymers of immunoglobulin G1 to human peripheral blood monocytes and polymorphonuclear leukocytes. J Clin Invest. 1982 Jan;69(1):1–8. [PMC free article] [PubMed]
  • Segal DM, Hurwitz E. Binding of affinity cross-linked oligomers of IgG to cells bearing Fc receptors. J Immunol. 1977 Apr;118(4):1338–1337. [PubMed]
  • Ory PA, Goldstein IM, Kwoh EE, Clarkson SB. Characterization of polymorphic forms of Fc receptor III on human neutrophils. J Clin Invest. 1989 May;83(5):1676–1681. [PMC free article] [PubMed]
  • Edberg JC, Redecha PB, Salmon JE, Kimberly RP. Human Fc gamma RIII (CD16). Isoforms with distinct allelic expression, extracellular domains, and membrane linkages on polymorphonuclear and natural killer cells. J Immunol. 1989 Sep 1;143(5):1642–1649. [PubMed]
  • Roos D, Bot AA, van Schaik ML, de Boer M, Daha MR. Interaction between human neutrophils and zymosan particles: the role of opsonins and divalent cations. J Immunol. 1981 Feb;126(2):433–440. [PubMed]
  • Ezekowitz RA, Sim RB, MacPherson GG, Gordon S. Interaction of human monocytes, macrophages, and polymorphonuclear leukocytes with zymosan in vitro. Role of type 3 complement receptors and macrophage-derived complement. J Clin Invest. 1985 Dec;76(6):2368–2376. [PMC free article] [PubMed]
  • Ross GD, Cain JA, Lachmann PJ. Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin as functions as a receptor for zymosan and rabbit erythrocytes as well as a receptor for iC3b. J Immunol. 1985 May;134(5):3307–3315. [PubMed]
  • Fleit HB, Wright SD, Unkeless JC. Human neutrophil Fc gamma receptor distribution and structure. Proc Natl Acad Sci U S A. 1982 May;79(10):3275–3279. [PMC free article] [PubMed]
  • Fanger MW, Shen L, Graziano RF, Guyre PM. Cytotoxicity mediated by human Fc receptors for IgG. Immunol Today. 1989 Mar;10(3):92–99. [PubMed]
  • Huizinga TW, van Kemenade F, Koenderman L, Dolman KM, von dem Borne AE, Tetteroo PA, Roos D. The 40-kDa Fc gamma receptor (FcRII) on human neutrophils is essential for the IgG-induced respiratory burst and IgG-induced phagocytosis. J Immunol. 1989 Apr 1;142(7):2365–2369. [PubMed]
  • Kimberly RP, Tappe NJ, Merriam LT, Redecha PB, Edberg JC, Schwartzman S, Valinsky JE. Carbohydrates on human Fc gamma receptors. Interdependence of the classical IgG and nonclassical lectin-binding sites on human Fc gamma RIII expressed on neutrophils. J Immunol. 1989 Jun 1;142(11):3923–3930. [PubMed]
  • Weinshank RL, Luster AD, Ravetch JV. Function and regulation of a murine macrophage-specific IgG Fc receptor, Fc gamma R-alpha. J Exp Med. 1988 Jun 1;167(6):1909–1925. [PMC free article] [PubMed]
  • Mellman I. Relationships between structure and function in the Fc receptor family. Curr Opin Immunol. 1988 Sep-Oct;1(1):16–25. [PubMed]
  • Stengelin S, Stamenkovic I, Seed B. Isolation of cDNAs for two distinct human Fc receptors by ligand affinity cloning. EMBO J. 1988 Apr;7(4):1053–1059. [PMC free article] [PubMed]
  • Hibbs ML, Bonadonna L, Scott BM, McKenzie IF, Hogarth PM. Molecular cloning of a human immunoglobulin G Fc receptor. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2240–2244. [PMC free article] [PubMed]
  • Brooks DG, Qiu WQ, Luster AD, Ravetch JV. 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. [PMC free article] [PubMed]
  • Selvaraj P, Rosse WF, Silber R, Springer TA. The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria. Nature. 1988 Jun 9;333(6173):565–567. [PubMed]
  • Simmons D, Seed B. The Fc gamma receptor of natural killer cells is a phospholipid-linked membrane protein. Nature. 1988 Jun 9;333(6173):568–570. [PubMed]
  • Huizinga TW, van der Schoot CE, Jost C, Klaassen R, Kleijer M, von dem Borne AE, Roos D, Tetteroo PA. The PI-linked receptor FcRIII is released on stimulation of neutrophils. Nature. 1988 Jun 16;333(6174):667–669. [PubMed]
  • Hogg N. The structure and function of Fc receptors. Immunol Today. 1988 Jul-Aug;9(7-8):185–187. [PubMed]
  • Hynes RO. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. [PubMed]
  • Graham IL, Gresham HD, Brown EJ. An immobile subset of plasma membrane CD11b/CD18 (Mac-1) is involved in phagocytosis of targets recognized by multiple receptors. J Immunol. 1989 Apr 1;142(7):2352–2358. [PubMed]
  • Schmalstieg FC, Rudloff HE, Anderson DC. Binding of the adhesive protein complex (LFA-1/Mac-1/p150,95) to concanavalin A. J Leukoc Biol. 1986 Feb;39(2):193–203. [PubMed]
  • Frank MM, Hamburger MI, Lawley TJ, Kimberly RP, Plotz PH. Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus. N Engl J Med. 1979 Mar 8;300(10):518–523. [PubMed]
  • Parris TM, Kimberly RP, Inman RD, McDougal JS, Gibofsky A, Christian CL. Defective Fc receptor-mediated function of the mononuclear phagocyte system in lupus nephritis. Ann Intern Med. 1982 Oct;97(4):526–532. [PubMed]
  • Kimberly RP, Meryhew NL, Runquist OA. Mononuclear phagocyte function in SLE. I. Bipartite Fc- and complement-dependent dysfunction. J Immunol. 1986 Jul 1;137(1):91–96. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...