Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1989 Jul 1;170(1):73–86. doi: 10.1084/jem.170.1.73

Murine natural killer cells express functional Fc gamma receptor II encoded by the Fc gamma R alpha gene

PMCID: PMC2189375  PMID: 2526196

Abstract

We report evidence that murine NK cells express a functional Fc gamma RII encoded by the Fc gamma RII alpha gene. Several lines of indirect evidence indicate that freshly obtained NK cells from mice of several strains bear a functional Fc gamma RII: (a) anti-Fc gamma RII antibody 2.4G2 detects a small but significant proportion of sIg- cells and a small proportion of the 2.4G2+ cells are included in the Thy-1+ population; (b) sIg- lymphocytes contain 2.4G2+ and Fc gamma R-bearing cells in similar proportions; (c) binding of particulate immune complexes by sIg- lymphocytes is completely inhibited by 2.4G2; (d) 2.4G2+ cells mediate greater than 50% of the spontaneous cytotoxicity in sIg- splenic lymphocytes. Direct evidence for the presence of Fc gamma RII on murine NK cells is provided by the results of two-color immunofluorescence studies performed on splenic lymphocytes from C57BL/6 mice showing coexpression of NK-1.1 and 2.4G2. Studies of in vitro propagated homogeneous NK cell populations confirm that murine NK cells express only Fc gamma RII and that this Fc gamma R is functional, as shown in experiments of inhibition of ADCC by the anti-Fc gamma RII antibody 2.4G2. The results of studies at the molecular level show that an Fc gamma RII alpha transcript identical to that expressed in macrophages is the only molecule encoding Fc gamma RII in murine NK cells.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anegón I., Cuturi M. C., Trinchieri G., Perussia B. Interaction of Fc receptor (CD16) ligands induces transcription of interleukin 2 receptor (CD25) and lymphokine genes and expression of their products in human natural killer cells. J Exp Med. 1988 Feb 1;167(2):452–472. doi: 10.1084/jem.167.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Austyn J. M., Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol. 1981 Oct;11(10):805–815. doi: 10.1002/eji.1830111013. [DOI] [PubMed] [Google Scholar]
  3. Beaumont T. J., Roder J. C., Elliott B. E., Kerbel R. S., Dennis J. W., Kasai M., Okumura K. Comparative analysis of cell surface markers on murine NK cells and CTL target-effector conjugates. Scand J Immunol. 1982 Aug;16(2):123–133. doi: 10.1111/j.1365-3083.1982.tb00706.x. [DOI] [PubMed] [Google Scholar]
  4. Biron C. A., Sonnenfeld G., Welsh R. M. Interferon induces natural killer cell blastogenesis in vivo. J Leukoc Biol. 1984 Jan;35(1):31–37. doi: 10.1002/jlb.35.1.31. [DOI] [PubMed] [Google Scholar]
  5. Biron C. A., Turgiss L. R., Welsh R. M. Increase in NK cell number and turnover rate during acute viral infection. J Immunol. 1983 Sep;131(3):1539–1545. [PubMed] [Google Scholar]
  6. Biron C. A., Welsh R. M. Blastogenesis of natural killer cells during viral infection in vivo. J Immunol. 1982 Dec;129(6):2788–2795. [PubMed] [Google Scholar]
  7. Biron C. A., van den Elsen P., Tutt M. M., Medveczky P., Kumar V., Terhorst C. Murine natural killer cells stimulated in vivo do not express the T cell receptor alpha, beta, gamma, T3 delta, or T3 epsilon genes. J Immunol. 1987 Sep 1;139(5):1704–1710. [PubMed] [Google Scholar]
  8. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  9. Diamond B., Yelton D. E. A new Fc receptor on mouse macrophages binding IgG3. J Exp Med. 1981 Mar 1;153(3):514–519. doi: 10.1084/jem.153.3.514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Hackett J., Jr, Bennett M., Kumar V. Origin and differentiation of natural killer cells. I. Characteristics of a transplantable NK cell precursor. J Immunol. 1985 Jun;134(6):3731–3738. [PubMed] [Google Scholar]
  12. Hackett J., Jr, Tutt M., Lipscomb M., Bennett M., Koo G., Kumar V. Origin and differentiation of natural killer cells. II. Functional and morphologic studies of purified NK-1.1+ cells. J Immunol. 1986 Apr 15;136(8):3124–3131. [PubMed] [Google Scholar]
  13. Herberman R. B., Bartram S., Haskill J. S., Nunn M., Holden H. T., West W. H. Fc receptors on mouse effector cells mediating natural cytotoxicity against tumor cells. J Immunol. 1977 Jul;119(1):322–326. [PubMed] [Google Scholar]
  14. Hibbs M. L., Walker I. D., Kirszbaum L., Pietersz G. A., Deacon N. J., Chambers G. W., McKenzie I. F., Hogarth P. M. The murine Fc receptor for immunoglobulin: purification, partial amino acid sequence, and isolation of cDNA clones. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6980–6984. doi: 10.1073/pnas.83.18.6980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Huizinga T. W., van der Schoot C. E., Jost C., Klaassen R., Kleijer M., von dem Borne A. E., Roos D., Tetteroo P. A. The PI-linked receptor FcRIII is released on stimulation of neutrophils. Nature. 1988 Jun 16;333(6174):667–669. doi: 10.1038/333667a0. [DOI] [PubMed] [Google Scholar]
  16. Koo G. C., Peppard J. R. Establishment of monoclonal anti-Nk-1.1 antibody. Hybridoma. 1984 Fall;3(3):301–303. doi: 10.1089/hyb.1984.3.301. [DOI] [PubMed] [Google Scholar]
  17. Kurlander R. J., Ellison D. M., Hall J. The blockade of Fc receptor-mediated clearance of immune complexes in vivo by a monoclonal antibody (2.4G2) directed against Fc receptors on murine leukocytes. J Immunol. 1984 Aug;133(2):855–862. [PubMed] [Google Scholar]
  18. Kurlander R. J., Hall J. Comparison of intravenous gamma globulin and a monoclonal anti-Fc receptor antibody as inhibitors of immune clearance in vivo in mice. J Clin Invest. 1986 Jun;77(6):2010–2018. doi: 10.1172/JCI112530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kuziel W. A., Takashima A., Bonyhadi M., Bergstresser P. R., Allison J. P., Tigelaar R. E., Tucker P. W. Regulation of T-cell receptor gamma-chain RNA expression in murine Thy-1+ dendritic epidermal cells. Nature. 1987 Jul 16;328(6127):263–266. doi: 10.1038/328263a0. [DOI] [PubMed] [Google Scholar]
  20. Lanier L. L., Le A. M., Phillips J. H., Warner N. L., Babcock G. F. Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol. 1983 Oct;131(4):1789–1796. [PubMed] [Google Scholar]
  21. Lanier L. L., Phillips J. H., Hackett J., Jr, Tutt M., Kumar V. Natural killer cells: definition of a cell type rather than a function. J Immunol. 1986 Nov 1;137(9):2735–2739. [PubMed] [Google Scholar]
  22. Lewis V. A., Koch T., Plutner H., Mellman I. A complementary DNA clone for a macrophage-lymphocyte Fc receptor. 1986 Nov 27-Dec 3Nature. 324(6095):372–375. doi: 10.1038/324372a0. [DOI] [PubMed] [Google Scholar]
  23. Mengle-Gaw L., McDevitt H. O. Isolation and characterization of a cDNA clone for the murine I-E beta polypeptide chain. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7621–7625. doi: 10.1073/pnas.80.24.7621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nathan C., Brukner L., Kaplan G., Unkeless J., Cohn Z. Role of activated macrophages in antibody-dependent lysis of tumor cells. J Exp Med. 1980 Jul 1;152(1):183–197. doi: 10.1084/jem.152.1.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Perussia B., Acuto O., Terhorst C., Faust J., Lazarus R., Fanning V., Trinchieri G. Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. II. Studies of B73.1 antibody-antigen interaction on the lymphocyte membrane. J Immunol. 1983 May;130(5):2142–2148. [PubMed] [Google Scholar]
  26. Perussia B., Fanning V., Trinchieri G. A human NK and K cell subset shares with cytotoxic T cells expression of the antigen recognized by antibody OKT8. J Immunol. 1983 Jul;131(1):223–231. [PubMed] [Google Scholar]
  27. Perussia B., Ramoni C., Anegon I., Cuturi M. C., Faust J., Trinchieri G. Preferential proliferation of natural killer cells among peripheral blood mononuclear cells cocultured with B lymphoblastoid cell lines. Nat Immun Cell Growth Regul. 1987;6(4):171–188. [PubMed] [Google Scholar]
  28. Perussia B., Starr S., Abraham S., Fanning V., Trinchieri G. Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. I. Characterization of the lymphocyte subset reactive with B73.1. J Immunol. 1983 May;130(5):2133–2141. [PubMed] [Google Scholar]
  29. Perussia B., Trinchieri G., Cerottini J. C. Analysis of human lymphocyte subpopulations responsible for antibody-dependent and spontaneous cell-mediated cytotoxicity. Transplant Proc. 1979 Mar;11(1):793–795. [PubMed] [Google Scholar]
  30. Phillips N. E., Parker D. C. Subclass specificity of Fc gamma receptor-mediated inhibition of mouse B cell activation. J Immunol. 1985 May;134(5):2835–2838. [PubMed] [Google Scholar]
  31. Ravetch J. V., Luster A. D., Weinshank R., Kochan J., Pavlovec A., Portnoy D. A., Hulmes J., Pan Y. C., Unkeless J. C. Structural heterogeneity and functional domains of murine immunoglobulin G Fc receptors. Science. 1986 Nov 7;234(4777):718–725. doi: 10.1126/science.2946078. [DOI] [PubMed] [Google Scholar]
  32. Selvaraj P., Rosse W. F., Silber R., Springer T. A. 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. doi: 10.1038/333565a0. [DOI] [PubMed] [Google Scholar]
  33. 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. doi: 10.1038/333568a0. [DOI] [PubMed] [Google Scholar]
  34. Suzuki R., Handa K., Itoh K., Kumagai K. Natural killer (NK) cells as a responder to interleukin 2 (IL 2). I. Proliferative response and establishment of cloned cells. J Immunol. 1983 Feb;130(2):981–987. [PubMed] [Google Scholar]
  35. Trinchieri G., Perussia B. Human natural killer cells: biologic and pathologic aspects. Lab Invest. 1984 May;50(5):489–513. [PubMed] [Google Scholar]
  36. Tutt M. M., Kuziel W. A., Hackett J., Jr, Bennett M., Tucker P. W., Kumar V. Murine natural killer cells do not express functional transcripts of the alpha-, beta-, or gamma-chain genes of the T cell receptor. J Immunol. 1986 Nov 1;137(9):2998–3001. [PubMed] [Google Scholar]
  37. Unkeless J. C. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J Exp Med. 1979 Sep 19;150(3):580–596. doi: 10.1084/jem.150.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Unkeless J. C., Scigliano E., Freedman V. H. Structure and function of human and murine receptors for IgG. Annu Rev Immunol. 1988;6:251–281. doi: 10.1146/annurev.iy.06.040188.001343. [DOI] [PubMed] [Google Scholar]
  39. Unkeless J. C. The presence of two Fc receptors on mouse macrophages: evidence from a variant cell line and differential trypsin sensitivity. J Exp Med. 1977 Apr 1;145(4):931–945. doi: 10.1084/jem.145.4.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Weinshank R. L., Luster A. D., Ravetch J. V. 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. doi: 10.1084/jem.167.6.1909. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES