Naturally occurring antibodies devoid of light chains

Abstract

RANDOM association of VL and VH repertoires contributes considerably to antibody diversity1. The diversity and the affinity are then increased by hypermutation in B cells located in germinal centres2. Except in the case of 'heavy chain' disease3, naturally occurring heavy-chain antibodies have not been described, although antigen binding has been demonstrated for separated heavy chains4 or cloned VH domains5. Here we investigate the presence of considerable amounts of IgG-like material of Mr 100K in the serum of the camel (Camelus dromedarius)6. These molecules are composed of heavy-chain dimers and are devoid of light chains, but nevertheless have an extensive antigen-binding repertoire, a finding that calls into question the role of light chains in the camel. Camel heavy-chain IgGs lack CH1, which in one IgG class might be structurally replaced by an extended hinge. Heavy-chain IgGs are a feature of all camelids. These findings open new perspectives in the engineering of antibodies.

Access 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

    Tonegawa, S. Nature 302, 575–581 (1983).

    ADS  CAS  Article  Google Scholar 

  2. 2

    Jacob, J., Kelsoe, G., Rajewski, K. & Weiss, U. Nature 354, 389–392 (1991).

    ADS  CAS  Article  Google Scholar 

  3. 3

    Fleischman, J. B., Pain, R. H. & Porter, R. R. Arch. Biochem. Biophys. Suppl. 1, 174–180 (1962).

    CAS  Google Scholar 

  4. 4

    Utsumi, S. & Karush, F. Biochemistry 3, 1329–1338 (1964).

    CAS  Article  Google Scholar 

  5. 5

    Ward, E. S., Güssow, D., Griffiths, A.D., Jones, P. T. & Winter, G. Nature 341, 544–546 (1989).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Ungar-Waron, H., Eliase, E., Gluckman, A. & Trainin, Z. Isr. J. vet. Med. 43, 198–203 (1987).

    Google Scholar 

  7. 7

    Bajyana Songa, E. & Hamers, R. Ann. Soc. Belge Méd. Trop. 68, 233–240 (1988).

    CAS  Google Scholar 

  8. 8

    Seligmann, M., Mihaesco, E., Preud'homme, J.-L., Danon, F. & Brouet, J.-C. Immun. Rev. 48, 145–167 (1979).

    CAS  Article  Google Scholar 

  9. 9

    Traunecker, A., Schneider, J., Kiefer, H. & Karjalaien, K. Nature 339, 68–70 (1989).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Henderschot, L. M., Bole, D., Köhler, G. & Kearney, J. F. J. Cell Biol. 104, 761–767 (1987).

    Article  Google Scholar 

  11. 11

    Henderschot, L. M. J. Cell Biol. 111, 829–837 (1990).

    Article  Google Scholar 

  12. 12

    Roholt, O., Onoue, K. & Pressman, D. Proc. natn. Acad. Sci. U.S.A. 51, 173–178 (1964).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Chothia, C., Novotny, J., Bruccoleri, R. & Karplus, M. J. molec. Biol. 186, 651–663 (1985).

    CAS  Article  Google Scholar 

  14. 14

    Kabat, E. A., Wu, T. T., Reid-Miller, M., Perry, H. M. & Gottesman, K. S. Sequences of Proteins of Immunological Interest 511 (US Dept of Health and Human Services, US Public Health Service, NIH, Bethesda, 1987).

    Google Scholar 

  15. 15

    Jackson, T., Morris, B. A. & Sanders, P. G. Molec. Immun. 29, 667–676 (1992).

    CAS  Article  Google Scholar 

  16. 16

    Poljak, R. J. et al. Proc. natn. Acad. Sci. U.S.A. 70, 3305–3310 (1973).

    ADS  CAS  Article  Google Scholar 

  17. 17

    Dangl, J. L., et al. EMBO J. 7, 1989–1994 (1988).

    CAS  Article  Google Scholar 

  18. 18

    Schneider, W. P. et al. Proc. natn. Acad. Sci. U.S.A. 85, 2509–2513 (1988).

    ADS  CAS  Article  Google Scholar 

  19. 19

    Evans, J. S. et al. FEBS Lett. 208, 211–216 (1986).

    CAS  Article  Google Scholar 

  20. 20

    Roditi, I. et al. J. Cell Biol. 108, 737–746 (1989).

    CAS  Article  Google Scholar 

  21. 21

    Dunnick, W., Rabbits, T. H. & Milstein, C. Nucleic Acids Res. 8, 1475–1484 (1980).

    CAS  Article  Google Scholar 

  22. 22

    Bülow, R., Nonnengässer, C. & Overath, P. Molec. Biochem. Parasitol. 32, 85–92 (1989).

    Article  Google Scholar 

  23. 23

    Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual 2nd edn (Cold Spring Harbor Laboratory Press, New York, 1989).

    Google Scholar 

  24. 24

    Sastry, L. et al. Proc. natn. Acad. Sci. U.S.A. 86, 5728–5732 (1989).

    ADS  CAS  Article  Google Scholar 

  25. 25

    Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    ADS  CAS  Article  Google Scholar 

  26. 26

    Klein, J. Immunology (Blackwell Scientific, London, 1990).

    Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hamers-Casterman, C., Atarhouch, T., Muyldermans, S. et al. Naturally occurring antibodies devoid of light chains. Nature 363, 446–448 (1993). https://doi.org/10.1038/363446a0

Download citation

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing