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Targeted disruption of µ chain membrane exon causes loss of heavy-chain allelic exclusion

Abstract

BURNET'S clonal selection theory1 suggests that each B lymphocyte is committed to a single antibody specificity. This is achieved by a programme of somatic rearrangements of the gene segments encoding antibody variable (V) regions, in the course of B-cell development2,3. Evidence from immunoglobulin-transgenic mice and immunoglobulin-gene-transfected transformed pre-B cells suggests that the membrane form of the immunoglobulin heavy (H) chain of class µ (µm), expressed from a rearranged H-chain (IgH) locus, may signal allelic exclusion of the homologous IgH locus in the cell4–6 and initiation of light (L)-chain gene rearrangement in the Ig/c loci6. We report here that targeted disruption of the membrane exon of the µ chain indeed results in the loss of H-chain allelic exclusion. But, some K chain gene rearrangement is still observed in the absence of µm expression.

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References

  1. Burnet, F. M. The Clonal Selection Theory of Acquired Immunity (Cambridge Univ. Press, 1959).

    Book  Google Scholar 

  2. Tonegawa, S. Nature 302, 79–84 (1983).

    Article  Google Scholar 

  3. Alt, F. W. et al. EMBO J. 3, 1209–1219 (1984).

    Article  CAS  Google Scholar 

  4. Nussenzweig, M. C. et al. Science 236, 816–819 (1987).

    Article  ADS  CAS  Google Scholar 

  5. Manz, J., Denis, K., Witte, O., Brinster, R. & Storb, U. J. exp. Med. 168, 1363–1381 (1988).

    Article  CAS  Google Scholar 

  6. Reth, M., Petrac, E., Wiese, P., Lobel, L. & Alt, F. W. EMBO J. 6, 3299–3305 (1987).

    Article  CAS  Google Scholar 

  7. Kitamura, D., Roes, J. Kühn, R. & Rajewsky, K. Nature 350, 423–426 (1991).

    Article  ADS  CAS  Google Scholar 

  8. Ichihara, Y., Hayashida, H., Miyazawa, S. & Kurosawa, Y. Eur. J. Immun. 19, 1847–1854 (1989).

    Article  Google Scholar 

  9. Gu, H., Kitamura, D. & Rajewsky, K. Cell 65, 47–54 (1991).

    Article  CAS  Google Scholar 

  10. Köhler, G., Proc natn. Acad. Sci. U.S.A. 77, 2197–2199 (1980).

    Article  ADS  Google Scholar 

  11. Radbruch, A., Müller, W. & Rajewsky, K. Proc. natn. Acad. Sci. U.S.A. 83, 3954–3957 (1986).

    Article  ADS  CAS  Google Scholar 

  12. Ferrier, P. et al. EMBO J. 9, 117–125 (1990).

    Article  CAS  Google Scholar 

  13. Jäck, H. M., Berg, J. & Wabl, M. Eur. J. Immun. 19, 843–847 (1989).

    Article  Google Scholar 

  14. Blackwell, T. K. et al. EMBO J. 8, 735–742 (1989).

    Article  CAS  Google Scholar 

  15. Schlissel, M. S. & Baltimore, D. Cell 58, 1001–1007 (1989).

    Article  CAS  Google Scholar 

  16. Cohn, M. & Langman, R. E. Immun. Rev. 115, 7–142 (1990).

    Article  Google Scholar 

  17. Pillai, S. & Baltimore, D. Curr. Topics microbiol. Immun. 137, 136–139 (1988).

    CAS  Google Scholar 

  18. Kerr, W. G. et al. Int. Immun. 1, 355–361 (1989).

    Article  CAS  Google Scholar 

  19. Karasuyama, H., Kudo, A. & Melchers, F. J. exp. Med. 172, 962–972 (1990).

    Article  Google Scholar 

  20. Tsubata, T. & Reth, M. J. exp. Med. 172, 973–976 (1990).

    Article  CAS  Google Scholar 

  21. Cherayll, B. J. & Pillai, S. J. exp. Med. 173, 111–116 (1991).

    Article  Google Scholar 

  22. Kubagawa, H., Cooper, M. D., Carroll, A. J. & Burrows, P. D. Proc. natn. Acad. Sci. U.S.A. 86, 2356–2360 (1989).

    Article  ADS  CAS  Google Scholar 

  23. Nishikawa, S., Sasaki, Y., Kina, T., Amagi, T. & Katsura, Y. Immunogenetics 23, 137–139 (1986).

    Article  CAS  Google Scholar 

  24. Schüppl, R., Wilke, J. & Weiler, E. Eur. J. Immun. 17, 739–741 (1987).

    Article  Google Scholar 

  25. Coffman, R. L. Immun. Rev. 69, 5–23 (1982).

    Article  CAS  Google Scholar 

  26. Grützmann, R. thesis, Univ. Cologne (1981).

  27. Hayashi, S. et al. J. exp. Med. 171, 1683–1695 (1990).

    Article  CAS  Google Scholar 

  28. McHeyzer-Williams, M. G. & Nossal, G. J. V. J. Immun. Meth. 119, 9–17 (1989).

    Article  CAS  Google Scholar 

  29. Oi, V. T. & Herzenberg, L. A. Molec. Immun. 16, 1005–1017 (1979).

    Article  CAS  Google Scholar 

  30. Förster, I., Vieira, P. & Rajewsky, K. Int. Immun. 1, 321–331 (1991).

    Article  Google Scholar 

  31. Gu, H., Förster, I. & Rajewsky, K. EMBO J. 9, 2133–2410 (1990).

    Article  CAS  Google Scholar 

  32. Gause, A., Yoshida, N., Kappen, C. & Rajewsky, K., Eur. J. Immun. 17, 981–990 (1987).

    Article  CAS  Google Scholar 

  33. Weiss, U. & Rajewsky, K. J. exp. Med. 172, 1681–1689 (1990).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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Kitamura, D., Rajewsky, K. Targeted disruption of µ chain membrane exon causes loss of heavy-chain allelic exclusion. Nature 356, 154–156 (1992). https://doi.org/10.1038/356154a0

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