Molecular and functional characteristics of the Fcα/μR, a novel Fc receptor for IgM and IgA

Review

Abstract

IgM is the first antibody to be produced in a humoral immune response and is a major isotope of natural antibodies and may play an important role in innate immunity. On the other hand, IgA is a secreted antibody at the mucosal membrane such as the gastrointestinal and respiratory tracts and protects from initial invasion of microbes. However, how these antibodies are involved in immunity has been poorly elucidated. We previously identified a novel Fc receptor for IgA and IgM, designated Fcα/μ receptor (Fcα/μR), whose gene is closely located at the polymeric immunoglobulin receptor (poly-IgR), also a receptor for IgA and IgM, in the Fc receptor gene cluster on the chromosome 1. In contrast to the the poly-IgR that is expressed on epithelial, but not hematopoietic, cells, Fcα/μR is constitutively expressed on the majority of B lymphocytes and macrophages in the spleen and at the center of the secondary lymphoid follicles. The Fcα/μR mediates endocytosis Staphylococcus aureus /anti-S. aureus IgM antibody immune complexes by B lymphocytes, for which the dileucine motif in the cytoplasmic tail of the mouse Fcα/μR is responsible. These results reveal a new mechanism in the primary stage of immune defense against microbes.

References

  1. 1.
    Aiken C, Konner J, Landau NR, Lenburg ME, Trono D (1994) Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell 76:853–864PubMedCrossRefGoogle Scholar
  2. 2.
    Boes M (2000) Role of natural and immune IgM antibodies in immune responses. Mol Immunol 37:1141–1149PubMedCrossRefGoogle Scholar
  3. 3.
    Boes M, Schmidt T, Linkemann K, Beaudette BC, Marshak-Rothstein A, Chen J (2000) Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. Proc Natl Acad Sci USA 97:1184–1189PubMedCrossRefGoogle Scholar
  4. 4.
    Carroll MC (1998) The role of complement and complement receptors in induction and regulation of immunity. Annu Rev Immunol 16:545–568PubMedCrossRefGoogle Scholar
  5. 5.
    Cho Y, Usui K, Honda S, Tahara-Hanaoka S, Shibuya K, Shibuya A (2006) Molecular characteristics of IgA and IgM Fc binding to the Fcalpha/muR. Biochem Biophys Res Commun 345:474–478PubMedCrossRefGoogle Scholar
  6. 6.
    Craig HM, Pandori MW, Guatelli JC (1998) Interaction of HIV-1 Nef with the cellular dileucine-based sorting pathway is required for CD4 down-regulation and optimal viral infectivity. Proc Natl Acad Sci USA 95:11229–11234PubMedCrossRefGoogle Scholar
  7. 7.
    Daeron M (1997) Fc receptor biology. Annu Rev Immunol 15:203–234PubMedCrossRefGoogle Scholar
  8. 8.
    Dombrowicz D, Flamand V, Brigman KK, Koller BH, Kinet JP (1993) Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor alpha chain gene. Cell 75:969–976PubMedCrossRefGoogle Scholar
  9. 9.
    Ehrenstein MR, O’Keefe TL, Davies SL, Neuberger MS (1998) Targeted gene disruption reveals a role for natural secretory IgM in the maturation of the primary immune response. Proc Natl Acad Sci USA 95:10089–10093PubMedCrossRefGoogle Scholar
  10. 10.
    Ehrenstein MR, Cook HT, Neuberger MS (2000) Deficiency in serum immunoglobulin (Ig)M predisposes to development of IgG autoantibodies. J Exp Med 191:1253–1258PubMedCrossRefGoogle Scholar
  11. 11.
    Ercolani L, Novogrodsky A, Suthanthiran M, Rubin AL, Stenzel KH (1981) Expression of Fc mu receptors by human T lymphocytes: effects of enzymes, metabolic inhibitors, and X-irradiation. J Immunol 127:2044–2051PubMedGoogle Scholar
  12. 12.
    Fujiwara H, Kikutani H, Suematsu S, Naka T, Yoshida K, Tanaka T, Suemura M, Matsumoto N, Kojima S et al (1994) The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice. Proc Natl Acad Sci USA 91:6835–6839PubMedCrossRefGoogle Scholar
  13. 13.
    Gabilondo AM, Hegler J, Krasel C, Boivin-Jahns V, Hein L, Lohse MJ (1997) A dileucine motif in the C terminus of the beta2-adrenergic receptor is involved in receptor internalization. Proc Natl Acad Sci USA 94:12285–12290PubMedCrossRefGoogle Scholar
  14. 14.
    Hamer I, Haft CR, Paccaud JP, Maeder C, Taylor S, Carpentier JL (1997) Dual role of a dileucine motif in insulin receptor endocytosis. J Biol Chem 272:21685–21691PubMedCrossRefGoogle Scholar
  15. 15.
    Hunziker W, Fumey C (1994) A di-leucine motif mediates endocytosis and basolateral sorting of macrophage IgG Fc receptors in MDCK cells. EMBO J 13:2963–2969PubMedGoogle Scholar
  16. 16.
    Kinet JP, Launay P (2000) Fc alpha/microR: single member or first born in the family? Nat Immunol 1:371–372PubMedCrossRefGoogle Scholar
  17. 17.
    Liblau RS, Bach JF (1992) Selective IgA deficiency and autoimmunity. Int Arch Allergy Immunol 99:16–27PubMedCrossRefGoogle Scholar
  18. 18.
    Maliszewski CR, March CJ, Schoenborn MA, Gimpel S, Shen L (1990) Expression cloning of a human Fc receptor for IgA. J Exp Med 172:1665–1672PubMedCrossRefGoogle Scholar
  19. 19.
    Mathur A, Lynch RG, Kohler G (1988) Expression, distribution and specificity of Fc receptors for IgM on murine B cells. J Immunol 141:1855–1862PubMedGoogle Scholar
  20. 20.
    McDonald KJ, Cameron AJ, Allen JM, Jardine AG (2002) Expression of Fc alpha/mu receptor by human mesangial cells: a candidate receptor for immune complex deposition in IgA nephropathy. Biochem Biophys Res Commun 290:438–442PubMedCrossRefGoogle Scholar
  21. 21.
    Mostov KE (1994) Transepithelial transport of immunoglobulins. Annu Rev Immunol 12:63–84PubMedCrossRefGoogle Scholar
  22. 22.
    Nakamura T, Kubagawa H, Ohno T, Cooper MD (1993) Characterization of an IgM Fc-binding receptor on human T cells. J Immunol 151:6933–6941PubMedGoogle Scholar
  23. 23.
    Ochsenbein AF, Fehr T, Lutz C, Suter M, Brombacher F, Hengartner H, Zinkernagel RM (1999) Control of early viral and bacterial distribution and disease by natural antibodies. Science 286:2156–2159PubMedCrossRefGoogle Scholar
  24. 24.
    Ohno T, Kubagawa H, Sanders SK, Cooper MD (1990) Biochemical nature of an Fc mu receptor on human B-lineage cells. J Exp Med 172:1165–1175PubMedCrossRefGoogle Scholar
  25. 25.
    Pricop L, Rabinowich H, Morel PA, Sulica A, Whiteside TL, Herberman RB (1993) Characterization of the Fc mu receptor on human natural killer cells. Interaction with its physiologic ligand, human normal IgM, specificity of binding, and functional effects. J Immunol 151:3018–3029PubMedGoogle Scholar
  26. 26.
    Rankin EC, Isenberg DA (1997) IgA deficiency and SLE: prevalence in a clinic population and a review of the literature. Lupus 6:390–394PubMedGoogle Scholar
  27. 27.
    Ravetch JV, Kinet JP (1991) Fc receptors. Annu Rev Immunol 9:457–492PubMedGoogle Scholar
  28. 28.
    Ravetch JV (1997) Fc receptors. Curr Opin Immunol 9:121–125PubMedCrossRefGoogle Scholar
  29. 29.
    Ravetch JV, Clynes RA (1998) Divergent roles for Fc receptors and complement in vivo. Annu Rev Immunol 16:421–432PubMedCrossRefGoogle Scholar
  30. 30.
    Sakamoto N, Shibuya K, Shimizu Y, Yotsumoto K, Miyabayashi T, Sakano S, Tsuji T, Nakayama E, Nakauchi H, Shibuya A (2001) A novel Fc receptor for IgA and IgM is expressed on both hematopoietic and non–hematopoietic tissues. Eur J Immunol 31:1310–1316PubMedCrossRefGoogle Scholar
  31. 31.
    Shibuya A, Sakamoto N, Shimizu Y, Shibuya K, Osawa M, Hiroyama T, Eyre HJ, Sutherland GR, Endo Y, Fujita T, Miyabayashi T, Sakano S, Tsuji T, Nakayama E, Phillips JH, Lanier LL, Nakauchi H (2000) Fc alpha/mu receptor mediates endocytosis of IgM-coated microbes. Nat Immunol 1:441–446PubMedCrossRefGoogle Scholar
  32. 32.
    Shimizu Y, Honda S, Yotsumoto K, Tahara-Hanaoka S, Eyre HJ, Sutherland GR, Endo Y, Shibuya K, Koyama A, Nakauchi H, Shibuya A (2001) Fc(alpha)/mu receptor is a single gene-family member closely related to polymeric immunoglobulin receptor encoded on Chromosome 1. Immunogenetics 53:709–711PubMedCrossRefGoogle Scholar
  33. 33.
    Stief A, Texido G, Sansig G, Eibel H, Le Gros G, van der Putten H (1994) Mice deficient in CD23 reveal its modulatory role in IgE production but no role in T and B cell development. J Immunol 152:3378–3390PubMedGoogle Scholar
  34. 34.
    Sylvestre DL, Ravetch JV (1994) Fc receptors initiate the Arthus reaction: redefining the inflammatory cascade. Science 265:1095–1098PubMedCrossRefGoogle Scholar
  35. 35.
    Takai T, Li M, Sylvestre D, Clynes R, Ravetch JV (1994) FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell 76:519–529PubMedCrossRefGoogle Scholar
  36. 36.
    Takai T, Ono M, Hikida M, Ohmori H, Ravetch JV (1996) Augmented humoral and anaphylactic responses in Fc gamma RII-deficient mice. Nature 379:346–349PubMedCrossRefGoogle Scholar
  37. 37.
    van de Winkel JG, Capel PJ (1993) Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications. Immunol Today 14:215–221PubMedCrossRefGoogle Scholar
  38. 38.
    Whelan CA (1981) A functional role for Fc mu receptors on human lymphocytes. Immunol Lett 3:249–254PubMedCrossRefGoogle Scholar
  39. 39.
    Yu P, Kosco-Vilbois M, Richards M, Kohler G, Lamers MC (1994) Negative feedback regulation of IgE synthesis by murine CD23. Nature 369:753–756PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences and Center for TARAUniversity of TsukubaTsukuba Science CityJapan

Personalised recommendations