Skip to main content

Thank you for visiting nature.com. 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.

  • Letter
  • Published:

Switch region of immunoglobulin Cμ gene is composed of simple tandem repetitive sequences

Abstract

Immunoglobulin heavy (H) chain genes comprise a family of variable region (V) genes and several constant region (C) genes which are classified, in mouse, into five major classes: μ, γ, α, δ and ε. During differentiation of a given B lymphocyte, a specific VH gene is first expressed as a part of the μ-chain and at a later stage the expressed H chain switches the C region from μ to γ or α without alteration of the VH region sequence1–3. This phenomenon, called immunoglobulin class switch, involves a unique recombination event that takes place at the region 5′ to each CH gene during B-lymphocyte differentiation4–6. The regions responsible for the class switch (or S–S) recombination are defined as switch (S) regions4. Recent structural analyses, which have revealed that S regions comprise tandem repetition of short unit sequences7–10, have allowed us to define the S region on a structural basis. The nudeotide sequences of S regions vary among different classes of CH gene, inevitably raising the possibility that the Sμ sequence contains separate subsets of sequences, each of which may pair with the S region of a different class. To test this possibility it is necessary to characterize the whole Sμ region. However, because the μ-gene clones isolated by other groups5,11,12 have lost a major portion (3 kilobases [kb]) of the central core of the Sμ region, only a small part of the Sμ region sequence has been determined8,10,12,13. We have now characterized the complete Sμ region by nudeotide sequence determination and restriction enzyme cleavage, and have found that it comprises simple tandem repetition of two kinds of 5-base pairs (bp) unit sequences, GAGCT and GGGGT. The nudeotide sequence of the Sμ region shares short common sequences with all the other S-region sequences. The results clearly exclude the above-mentioned possibility and support the proposal7,9,10,13 that S–S recombination is mediated by repetitive homologous short sequences.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Nossal, G. J. V., Warner, N. L. & Lewis, H. Cell. Immun. 2, 41–53 (1971).

    Article  CAS  Google Scholar 

  2. Pernis, B., Forni, L. & Amante, L. Ann. N.Y. Acad. Sci. 190, 420–431 (1971).

    Article  ADS  CAS  Google Scholar 

  3. Cooper, M. D., Kearney, J. F., Lydyard, P. M., Grossi, C. E. & Lanton, A. R. Cold Spring Harb. Symp. quant. Biol. 41, 139 (1976).

    Article  Google Scholar 

  4. Kataoka, T., Kawakami, T., Takahashi, N. & Honjo, T. Proc. natn. Acad. Sci. U.S.A. 77, 919–923 (1980).

    Article  ADS  CAS  Google Scholar 

  5. Davis, M. M. et al. Nature 283, 733–739 (1980).

    Article  ADS  CAS  Google Scholar 

  6. Maki, R., Traunecker, A., Sakano, H., Roeder, W. & Tonegawa, S. Proc. natn. Acad. Sci. USA. 77, 2138–2142 (1980).

    Article  ADS  CAS  Google Scholar 

  7. Kataoka, T., Miyata, T. & Honjo, T. Cell 23, 357–368 (1981).

    Article  CAS  Google Scholar 

  8. Davis, M. M., Kim, S. K. & Hood, L. Science 209, 1360–1365 (1980).

    Article  ADS  CAS  Google Scholar 

  9. Obata, M. et al. Proc. natn. Acad. Sci. U.S.A. 78, 2437–2441 (1981).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  11. Marcu, K. B., Banerji, J., Penncavage, N. A., Lang, R. & Arnheim, M. Cell 22, 187–196 (1980).

    Article  CAS  Google Scholar 

  12. Sakano, H., Maki, R., Kurosawa, Y., Roeder, W. & Tonegawa, S. Nature 286, 676–683 (1980).

    Article  ADS  CAS  Google Scholar 

  13. Takahashi, N., Kataoka, T. & Honjo, T. Gene 11, 117–127 (1980).

    Article  CAS  Google Scholar 

  14. Kawakami, T., Takahashi, N. & Honjo, T. Nucleic Acids Res. 8, 3933–3945 (1980).

    Article  CAS  Google Scholar 

  15. Maxam, A. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 560–564 (1977).

    Article  ADS  CAS  Google Scholar 

  16. Farabaugh, P. J. & Miller, J. H. J. molec. Biol. 126, 847–863 (1978).

    Article  CAS  Google Scholar 

  17. Honjo, T. & Kataoka, T. Proc. natn. Acad. Sci. U.S.A. 75, 2140–2144 (1978).

    Article  ADS  CAS  Google Scholar 

  18. Yaoita, Y. & Honjo, T. Nature 286, 850–853 (1980).

    Article  ADS  CAS  Google Scholar 

  19. Yaoita, Y. & Honjo, T. Biomed. Res. 1, 164–175 (1980).

    Article  CAS  Google Scholar 

  20. Coleclough, C., Cooper, C. & Perry, R. P. Proc. natn. Acad. Sa. U.S.A. 77, 1422–1426 (1980).

    Article  ADS  CAS  Google Scholar 

  21. Cory, S., Jackson, J. & Adams, J. M. Nature 285, 450–456 (1980).

    Article  ADS  CAS  Google Scholar 

  22. Rabbitts, T. H., Forster, A., Dunnick, W. & Bentley, D. L. Nature 283, 351–356 (1980).

    Article  ADS  CAS  Google Scholar 

  23. Sakano, H., Huppi, K., Heinrich, G. & Tonegawa, S. Nature 280, 288–294 (1978).

    Article  ADS  Google Scholar 

  24. Seidman, J. G. et al. Proc. natn. Acad. Sci. U.S.A. 77, 6022–6026 (1980).

    Article  ADS  CAS  Google Scholar 

  25. Clewell, D. & Helinski, D. Proc. natn. Acad. Sci. U.S.A. 62, 1159–1166 (1969).

    Article  ADS  CAS  Google Scholar 

  26. Honjo, T. et al. Cell 18, 559–568 (1979).

    Article  CAS  Google Scholar 

  27. Kataoka, T., Yamawaki-Kataoka, Y., Yamagishi, H. & Honjo, T. Proc. natn. Acad. Sci. U.S.A. 76, 4240–4244 (1979).

    Article  ADS  CAS  Google Scholar 

  28. Nishida, Y. et al. Proc. natn. Acad. Sci. U.S.A. 78, 1581–1585 (1981).

    Article  ADS  CAS  Google Scholar 

  29. Maniatis, T., Jeffrey, A. & Kleid, D. K. Proc natn. Acad.Sci. U.S.A. 72, 1184–1188 (1975).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nikaido, T., Nakai, S. & Honjo, T. Switch region of immunoglobulin Cμ gene is composed of simple tandem repetitive sequences. Nature 292, 845–848 (1981). https://doi.org/10.1038/292845a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/292845a0

This article is cited by

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

Quick links

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