Subjects

Abstract

IgM is the first antibody to be produced in a humoral immune response and plays an important role in the primary stages of immunity. Here we describe a mouse Fc receptor, designated Fcα/μR, and its human homolog, that bind both IgM and IgA with intermediate or high affinity. Fcα/μR is constitutively expressed on the majority of B lymphocytes and macrophages. Cross-linking Fcα/μR expressed on a pro-B cell line Ba/F3 transfectant with soluble IgM or IgM-coated microparticles induced internalization of the receptor. Fcα/μR also mediated primary B lymphocyte endocytosis of IgM-coated Staphylococcus aureus. Thus, Fcα/μR is involved in the primary stages of the immune response to microbes.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & Divergent roles for Fc receptors and complement in vivo. Annu. Rev. Immunol. 16, 421–432 (1998).

  2. 2.

    Fc receptors. Curr. Opin. Immunol. 9, 121 –5 (1997).

  3. 3.

    Fc receptor biology. Annu. Rev. Immunol. 15, 203–234 (1997).

  4. 4.

    et al. Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor α chain gene. Cell 75, 969–976 (1993).

  5. 5.

    et al. FcR γ chain deletion results in pleiotrophic effector cell defects. Cell 76, 519–529 (1994).

  6. 6.

    & Fc receptors initiate the Arthus reaction: Redefining the inflamatory cascade. Science 265, 1095–1098 ( 1994)

  7. 7.

    et al. Augmented humoral and anaphylactic responses in Fcγ RII-deficient mice. Nature 379, 346–349 (1996).

  8. 8.

    et al. Negative feedback regulation of IgE synthesis by murine CD23. Nature 369, 753–756 ( 1994).

  9. 9.

    et al. Mice deficient in CD23 reveal its modulatory role in IgE production but no role in T and B cell development. J. Immunol. 152, 3378–3390 (1994).

  10. 10.

    et al. The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice. Proc. Natl Acad. Sci. USA 91, 6835–6839 (1994).

  11. 11.

    et al. Control of early viral and bacterial distribution and disease by natural antibodies. Science 286, 2156 –2159 (1999).

  12. 12.

    A functional role for Fcμ receptors on human lymphocytes. Immunol. Lett. 3, 249–254 ( 1981).

  13. 13.

    et al. Expression of Fc mu receptors by human T lymphocytes: effects of enzymes, metabolic inhibitors, and X-irradiation. J. Immunol. 127, 2044–2051 ( 1981).

  14. 14.

    , & Expression, distribution and specificity of Fc receptors for IgM on murine B cells. J. Immunol. 141, 1855–1862 (1988).

  15. 15.

    , , & Biochemical nature of a Fcμ receptor on human B-lineage cells. J. Exp. Med. 172, 1165–1175 (1990).

  16. 16.

    , , & Characterization of an IgM Fc-binding receptor on human T cells. J. Immunol. 151, 6933–6941 (1993).

  17. 17.

    et al. Characterization of the Fcμ receptor on human natural killer cells. Interaction with its physiologic ligand, human normal IgM, specificity of binding, and functional effects. J. Immunol. 151 , 3018–3029 (1993).

  18. 18.

    Transepithelial transport of immunoglobulins. Annu. Rev. Immunol. 12, 63–84 ( 1994).

  19. 19.

    et al. Expression cloning of a human Fc receptor for IgA. J. Exp. Med. 172, 1665–1672 (1990).

  20. 20.

    et al. Reassessment of two apparent deletions of chromosome 16p to an ins (11;16) and at (1;16) by chromosome painting. Ann. Genet. 33, 219221 (1990).

  21. 21.

    GenomeNet WWW Server, http://www.genome.ad.jp/kegg2.html

  22. 22.

    , & Characterization of a critical binding site for human polymeric Immunoglobulin on secretory component. J. Immunol. 147, 3419–3426 (1991).

  23. 23.

    , , & A conserved binding site on the receptor for polymeric Ig is homologous to CDR1 of Ig Vκ domains. J. Immunol. 151, 1346–1352 (1993).

  24. 24.

    , , & Fine specificity of ligand-binding domain 1 in the polymeric Ig receptor: importance of the CDR2-containing region for IgM interaction. J. Immunol. 162, 6046–6052 (1999).

  25. 25.

    et al. Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell 76, 853–864 (1994).

  26. 26.

    et al. Dual role of a dileucine motif in insulin receptor endocytosis . J. Biol. Chem. 272, 21685– 21691 (1997).

  27. 27.

    et al. A dileucine motif in the C terminus of the β2-adrenergic receptor is involved in receptor internalization. Proc. Natl Acad. Sci. USA 94, 12285–12290 (1997).

  28. 28.

    , & 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– 11234 (1998).

  29. 29.

    & A di-leucine motif mediates endocytosis and basolateral sorting of macrophage IgG Fc receptors in MDCK cells. EMBO J. 13, 2963–2967 ( 1994).

  30. 30.

    et al. Enhancement antigen presentation using human Fcγ receptor (monocyte/macrophage)-specific immunogens. J. Immunol. 149, 3477–3481 (1992).

  31. 31.

    et al. Tyrosine-containing motif that transduces cell activation signals also determines internalization and antigen presentation via type III receptors for IgG. Nature 358, 337– 341 (1992).

  32. 32.

    , , & Immobilization and internalization of mutated IgE receptors in transfected cells. J. Immunol. 146, 958– 966 (1991).

  33. 33.

    et al. Altered expression of monocyte IgA Fc receptors is associated with defective endocytosis in patients with alcoholic cirrhosis: potential role for IFN-γ. J. Immunol. 155, 1606 –1612 (1995).

  34. 34.

    et al. Two distinct regions of FcγRI initiate separate signaling pathways involved in endocytosis and phagocytosis. EMBO J. 14, 432–441 (1995).

  35. 35.

    , , & Targeted gene disruption reveals a role for natural secretory IgM in the maturation of the primary immune response. Proc. Natl Acad. Sci. USA. 95, 10089–10093 (1998).

  36. 36.

    et al. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity 4, 573 –581 (1996).

  37. 37.

    et al. Physical and functional association of LFA-1 with DNAM-1 adhesion molecule. Immunity 11, 615– 623 (1999).

Download references

Acknowledgements

We thank A. Iwama, Y. Nakamura, H. Ema, M. Onodera, H. Miyoshi for discussions; Y. Morita and R. Shimamura for assistance with flow cytometry; and M. Ito for secretarial assistance. Supported in part by grants from the Sandler Family Supporting Foundation (to L. L. L.), the Ministry of Education, Science and Culture of Japan (to A. S.), and the Wellcome Trust and the National Health and Medical Research Council of Australia (to G. R. S.). DNAX Research Institute is supported by Schering-Plough Corporation (NJ).

Author information

Affiliations

  1. Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan.

    • Akira Shibuya
    • , Norihisa Sakamoto
    • , Yoshio Shimizu
    • , Kazuko Shibuya
    • , Mitsujiro Osawa
    • , Takashi Hiroyama
    •  & Hiromitsu Nakauchi
  2. TOREST (JST), 1-1-1 Tennodai, Tsukuba Science City, Ibaraki 305-8575, Japan.

    • Akira Shibuya
  3. CREST (JST), 1-1-1 Tennodai, Tsukuba Science City, Ibaraki 305-8575, Japan.

    • Hiromitsu Nakauchi
  4. Department of Parasitology and Immunology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.

    • Akira Shibuya
    • , Norihisa Sakamoto
    • , Kazuko Shibuya
    •  & Eiichi Nakayama
  5. First Department of Medicine, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.

    • Norihisa Sakamoto
    •  & Takao Tsuji
  6. Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, Adelaide, South Australia 5006, Australia.

    • Helen J. Eyre
    •  & Grant R. Sutherland
  7. Department of Biochemistry II, Fukushima Medical University, Hikarigaoka, 1, Fukushima 960-1295, Japan.

    • Yuichi Endo
    •  & Teizo Fujita
  8. The Second Research Department, Central Technology Laboratory, Asahi Chemical Industry Co. Ltd., 2-1 Samejima, Fuji, Shizuoka 416-8501, Japan.

    • Tomoyuki Miyabayashi
    •  & Seiji Sakano
  9. Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, 901 California Avenue, Palo Alto, CA 94304, USA.

    • Joseph H. Phillips
    •  & Lewis L. Lanier
  10. University of California San Francisco, Department of Microbiology and Immunology and the Cancer Research Institute, 513 Parnassus Avenue, Box 0414, San Francisco, CA 94143-0414, USA.

    • Lewis L. Lanier

Authors

  1. Search for Akira Shibuya in:

  2. Search for Norihisa Sakamoto in:

  3. Search for Yoshio Shimizu in:

  4. Search for Kazuko Shibuya in:

  5. Search for Mitsujiro Osawa in:

  6. Search for Takashi Hiroyama in:

  7. Search for Helen J. Eyre in:

  8. Search for Grant R. Sutherland in:

  9. Search for Yuichi Endo in:

  10. Search for Teizo Fujita in:

  11. Search for Tomoyuki Miyabayashi in:

  12. Search for Seiji Sakano in:

  13. Search for Takao Tsuji in:

  14. Search for Eiichi Nakayama in:

  15. Search for Joseph H. Phillips in:

  16. Search for Lewis L. Lanier in:

  17. Search for Hiromitsu Nakauchi in:

Corresponding author

Correspondence to Akira Shibuya.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/80886

Further reading