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Targeting of non-lg sequences in place of the V segment by somatic hyper mutation
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  • Published: 20 July 1995

Targeting of non-lg sequences in place of the V segment by somatic hyper mutation

  • J. Yélamos1,
  • N. Klix1,
  • B. Goyenechea1,
  • F. Lozano1 nAff2,
  • Y. L. Chui1 nAff3,
  • A. GonzÃlez FernÃndez1,
  • R. Pannell1,
  • M. S. Neuberger1 &
  • …
  • C. Milstein1 

Nature volume 376, pages 225–229 (1995)Cite this article

  • 413 Accesses

  • 208 Citations

  • 12 Altmetric

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Abstract

Affinity maturation of antibodies is characterized by localized hypermutation of the DNA around the V segment. Here we show, using mice containing single or multiple transgene constructs, that an immunoglobulin VK segment can be replaced by human β-globin or prokaryotic neo or gpt genes without affecting the rate of hypermutation; the V gene itself is not necessary for recruiting hypermutation. The ability to target hypermutation to heterologous genes in vivo could find more general applications in biology.

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References

  1. Griffiths, G. M., Berek, C., Kaartinen, M. & Milstein, C. Nature 312, 271–275 (1984).

    Article  ADS  CAS  Google Scholar 

  2. Berek, C., Berger, A. & Apel, M. Cell 67, 1121–1129 (1991).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  4. MacLennan, I. C., Liu, Y. J. & Johnson, G. D. Immun. Rev. 126, 143–161 (1992).

    Article  CAS  Google Scholar 

  5. Kuppers, R., Zhao, M., Hansmann, M. L. & Rajewsky, K. EMBO J. 12, 4955–4967 (1993).

    Article  CAS  Google Scholar 

  6. Pascual, V. et al. J. exp. Med. 180, 329–339 (1994).

    Article  CAS  Google Scholar 

  7. Gearhart, P. J. & Bogenhagen, D. F. Proc. natn. Acad. Sci. U.S.A. 80, 3439–3443 (1983).

    Article  ADS  CAS  Google Scholar 

  8. Lebécque, S. G. & Gearhart, P. J. J. exp. Med. 172, 1717–1727 (1990).

    Article  Google Scholar 

  9. Both, G. W., Taylor, L., Pollard, J. W. & Steele, E. J. Molec. cell. Biol. 10, 5187–5196 (1990).

    Article  CAS  Google Scholar 

  10. Weber, J. S., Berry, J., Manser, T. & Claflin, J. L. J. Immun. 146, 3652–3655 (1991).

    CAS  PubMed  Google Scholar 

  11. González-Fernández, A., Gupta, S. K., Pannell, R., Neuberger, M. S. & Milstein, C. Proc. natn. Acad. Sci. U.S.A. 91, 12614–12618 (1994).

    Article  ADS  Google Scholar 

  12. Motoyama, N., Okada, H. & Azuma, T. Proc. natn. Acad. Sci. U.S.A. 88, 7933–7937 (1991).

    Article  ADS  CAS  Google Scholar 

  13. O'Brien, R. L., Brinster, R. L. & Storb, U. Nature 326, 405–409 (1987).

    Article  ADS  CAS  Google Scholar 

  14. Sharpe, M. J., Milstein, C., Jarvis, J. M. & Neuberger, M. S. EMBO J. 10, 2139–2145 (1991).

    Article  CAS  Google Scholar 

  15. Rabbitts, T. H., Hamlyn, P. H. & Baer, R. Nature 306, 760–765 (1983).

    Article  ADS  CAS  Google Scholar 

  16. Umar, A., Schweitzer, P. A., Levy, N. S., Gearhart, J. D. & Gearhart, P. J. Proc. natn. Acad. Sci. U.S.A. 88, 4902–4906 (1991).

    Article  ADS  CAS  Google Scholar 

  17. Hackett, J. J., Stebbins, C., Rogerson, B., Davis, M. M. & Storb, U. J. exp. Med. 176, 225–231 (1992).

    Article  CAS  Google Scholar 

  18. Azuma, T., Motoyama, N., Fields, L. E. & Loh, D. Y. Int. Immun. 5, 121–130 (1993).

    Article  CAS  Google Scholar 

  19. Lozano, F., Maertzdorf, B., Pannell, R. & Milstein, C. EMBO J. 13, 4617–4622 (1994).

    Article  CAS  Google Scholar 

  20. Betz, A. G. et al. Cell 77, 239–248 (1994).

    Article  CAS  Google Scholar 

  21. González-Fernández, A. & Milstein, C. Proc. natn. Acad. Sci. U.S.A. 90, 9862–9866 (1993).

    Article  ADS  Google Scholar 

  22. Rada, C., González-Fernández, A., Jarvis, J. M. & Milstein, C. Eur. J. Immun. 24, 1453–1457 (1994).

    Article  CAS  Google Scholar 

  23. Berek, C. & Milstein, C. Immun. Rev. 96, 23–41 (1987).

    Article  CAS  Google Scholar 

  24. Lozano, F., Rada, C., Jarvis, J. M. & Milstein, C. Nature 363, 271–273 (1993).

    Article  ADS  CAS  Google Scholar 

  25. Rogerson, B., Hackett, J. J., Peters, A., Haasch, D. & Storb, U. EMBO J. 10, 4331–4341 (1991).

    Article  CAS  Google Scholar 

  26. Weigert, M. Prog. Immun. 6, 139–144 (1986).

    Google Scholar 

  27. Kocks, C. & Rajewsky, K. Proc. natn. Acad. Sci. U.S.A. 85, 8206–8210 (1988).

    Article  ADS  CAS  Google Scholar 

  28. Kepler, T. B. & Perelson, A. S. Immun. Today 14, 412–415 (1993).

    Article  CAS  Google Scholar 

  29. Rothenfluh, H. S., Taylor, L., Bothwell, A. L., Both, G. W. & Steele, E. J. Eur. J. Immun. 23, 2152–2159 (1993).

    Article  CAS  Google Scholar 

  30. Betz, A. G., Rada, C., Pannell, R., Milstein, C. & Neuberger, M. S. Proc. natn. Acad. Sci. U.S.A. 90, 2385–2388 (1993).

    Article  ADS  CAS  Google Scholar 

  31. Weber, J. S., Berry, J., Manser, T. & Claflin, J. L. J. Immun. 153, 3594–3602 (1994).

    CAS  PubMed  Google Scholar 

  32. Manser, T. in Somatic Hypermutation in V-regions (ed. Steele, E. J.) 20–25 (CRC, Boca Raton, FL, 1990).

    Google Scholar 

  33. Betz, A. G., Neuberger, M. S. & Milstein, C. C. Immun. Today 14, 405–411 (1993).

    Article  CAS  Google Scholar 

  34. Chui, Y. L., Lozano, F., Jarvis, J. M., Pannell, R. & Milstein, C. J. molec. Biol. 249, 555–563 (1995).

    Article  CAS  Google Scholar 

  35. Rogozin, I. B. & Kolchanov, N. A. Biochim. biophys. Acta 1171, 11–18 (1992).

    Article  CAS  Google Scholar 

  36. Steele, E. J., Rothenfluh, H. S. & Both, G. W. Immun. Cell Biol. 70, 129–144 (1992).

    Article  CAS  Google Scholar 

  37. Neuberger, M. S. & Milstein, C. Curr. Opin. Immun. 7, 248–254 (1995).

    Article  CAS  Google Scholar 

  38. Pettersson, S., Sharpe, M. J., Gilmore, D. R., Surani, M. A. & Neuberger, M. S. Int. Immun. 1, 509–516 (1989).

    Article  CAS  Google Scholar 

  39. Galfré, G. & Milstein, C. Meth. Enzym. 73, 3–46 (1981).

    Article  Google Scholar 

  40. Clackson, T. & Winter, G. Nucleic Acids Res. 17, 10163–10170 (1989).

    Article  CAS  Google Scholar 

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Author information

Author notes
  1. F. Lozano

    Present address: Servicio de Immunologia, Hospital Clinico y Provi-cial de Barcelona, Vlillaroel 170, Barcelona, 08036, Spain

  2. Y. L. Chui

    Present address: Clinical Immunology Unit, Department of Medicine, Prince of Wales Hospital, Shatin, N.T., Hong Kong

Authors and Affiliations

  1. Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

    J. Yélamos, N. Klix, B. Goyenechea, F. Lozano, Y. L. Chui, A. GonzÃlez FernÃndez, R. Pannell, M. S. Neuberger & C. Milstein

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  1. J. Yélamos
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Yélamos, J., Klix, N., Goyenechea, B. et al. Targeting of non-lg sequences in place of the V segment by somatic hyper mutation. Nature 376, 225–229 (1995). https://doi.org/10.1038/376225a0

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  • Received: 12 May 1995

  • Accepted: 12 June 1995

  • Issue date: 20 July 1995

  • DOI: https://doi.org/10.1038/376225a0

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