Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Inherited deletion of immunoglobulin heavy chain constant region genes in normal human individuals


The existence of specific probes for human genes makes it feasible to study genetic abnormalities, both inherited and acquired, at the level of the genome. In this respect, the antibody genes of man are of particular interest as they represent a multigene family expressed in many leukaemias and immunodeficiency diseases. Furthermore, selective deficiency of immunoglobulins has been described in healthy individuals1. Normally, human adults express five types of immunoglobulin—IgM, IgD, IgG, IgE and IgA (defined by the class of heavy chain constant region). Subclasses are also known in IgG (IgG1, IgG2, IgG3 and IgG4) and IgA (IgA1 and IgA2) in which the immunoglobulins contain γ1, γ2, γ3 or γ4 and α1 or α2 CH regions, respectively. Recently, a healthy Tunisian person was described who showed abnormal patterns of immunoglobulin expression2. The serum immunoglobulin of this individual, designated TAK3, was confined to IgM, IgD, IgG3, IgE and IgA2. We have now used cloned CH-gene probes to study the DNA of TAK3 as well as two brothers, also Tunisian but apparently unrelated to the individual TAK3, and who show a similar immunoglobulin abnormality. We found that in these cases there seems to have been a large chromosomal deletion which includes three γ genes, an α gene and a pseudo-ε gene. This deletion accounts for the simultaneous absence of certain H-chain subclasses. These results illustrate that the human immunoglobulin gene locus is capable of undergoing rapid change, which is particularly apparent within small populations in which consanguinity is common.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Van Loghem, E. et al. J. Immunogenet. 7, 285–299 (1980).

    CAS  Article  Google Scholar 

  2. 2

    Lefranc, G. et al. Eur. J. Immun. (in the press).

  3. 3

    Krawinkel, U. & Rabbitts, T. H. EMBO J. 1, 403–407 (1982).

    CAS  Article  Google Scholar 

  4. 4

    Takahashi, N. et al. Cell 29, 671–679 (1982).

    CAS  Article  Google Scholar 

  5. 5

    Croce, C. M. et al. Proc. natn. Acad. Sci. U.S.A. 76, 3416–3419 (1979).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Hobart, M. J. et al. Ann. hum. Genet. 45, 331–335 (1981).

    CAS  Article  Google Scholar 

  7. 7

    Kirsch, I. R., Morton, C. C., Nakahara, K. & Leder, P. Science 216, 301–303 (1982).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Rabbitts, T. H., Forster, A. & Milstein, C. P. Nucleic Acids Res. 9, 4509–4524 (1981).

    CAS  Article  Google Scholar 

  9. 9

    Flanagan, J. G. & Rabbitts, T. H. EMBO J. 1, 655–659 (1982).

    CAS  Article  Google Scholar 

  10. 10

    Flanagan, J. G. & Rabbitts, T. H. Nature 300, 709–713 (1982).

    ADS  CAS  Article  Google Scholar 

  11. 11

    Max, E. E., Battey, J., Ney, R., Kirsch, I. & Leder, P. Cell 129, 691–699 (1982).

    Article  Google Scholar 

  12. 12

    Nishida, Y., Miki, T., Hisajuma, H. & Honjo, T. Proc. natn. Acad. Sci. U.S.A. 79, 3833–3837 (1982).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Dunnick, W., Rabbitts, T. H. & Milstein, C. Nature 286, 669–675 (1980).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Southern, E. M. J. molec. Biol. 98, 503–517 (1975).

    CAS  Article  Google Scholar 

  15. 15

    Lefranc, E. M. et al. J. Immunogenet. 9, 1–9 (1982).

    CAS  Article  Google Scholar 

  16. 16

    Jeffreys, A. J. & Flavell, R. A. Cell 12, 429–439 (1977).

    CAS  Article  Google Scholar 

  17. 17

    Denhardt, D. T. Biochem. biophys. Res. Commun. 23, 641–646 (1966).

    CAS  Article  Google Scholar 

  18. 18

    Laskey, R. A. & Mills, A. D. FEBS Lett. 82, 314–316 (1977).

    CAS  Article  Google Scholar 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lefranc, MP., Lefranc, G. & Rabbitts, T. Inherited deletion of immunoglobulin heavy chain constant region genes in normal human individuals. Nature 300, 760–762 (1982).

Download citation

Further reading


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.


Quick links