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Immunoglobulin heavy-chain switching in pre-B leukaemias

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Abstract

Immunoglobulin gene expression is initiated in pre-B cells by rearrangements of heavy-chain variable genes V, D and J, for transcription together with the constant region gene Cμ (refs 1–7). The subsequent joining of light-chain V–J genes in the κ or λ families8,9 leads to formation of complete IgM molecules, which are then expressed on the surface of B cells. Heavy-chain isotype switching has been thought to occur later and to involve CH gene rearrangement via deletion of DNA between a switch site 5′ to Cμ and a switch site 5′ to the downstream Cγ, Cε or Cα gene expressed by a mature plasma cell10–15. On the other hand, isotype switching has been seen in human pre-B-cell leukaemias16,17 and in a murine pre-B-cell line before light-chain gene rearrangements and without Cμ gene deletion18,19. To explore further the isotype switching in pre-B cells, we used monoclonal antibodies in immunofluorescence assays to allow unambiguous assignment of the heavy-chain isotypes expressed by individual leukaemic cells in 11 pre-B-cell leukaemias. Switching in these leukaemic clones invariably led to expression of γ1 heavy-chain and κ light-chain determinants, occasionally together with γ4 and α. These results indicate a nonrandom order for heavy-chain isotype switching and for light-chain isotype expression, and also suggest that a mechanism exists for coordinating the two events.

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References

  1. Cooper, M. D. J. clin. Immun. 1, 81–89 (1981).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  4. Maki, R., Kearney, J. F., Paige, C. & Tonegawa, S. Science 209, 1366–1369 (1980).

    Article  ADS  CAS  Google Scholar 

  5. Perry, R. P., Kelley, D. E., Coleclough, C. & Kearney, J. F. Proc. natn. Acad. Sci. U.S.A. 78, 247–251 (1980).

    Article  ADS  Google Scholar 

  6. Alt, F., Rosenberg, N., Lewis, S., Thomas, E. & Baltimore, D. Cell 27, 381–390 (1981).

    Article  CAS  Google Scholar 

  7. Korsmeyer, S. J. et al. Proc. natn. Acad. Sci. U.S.A. 78, 7096–7100 (1981).

    Article  ADS  CAS  Google Scholar 

  8. Hieter, P. A., Korsmeyer, S. J., Waldmann, T. A. & Leder, P. Nature 290, 368–372 (1981).

    Article  ADS  CAS  Google Scholar 

  9. Coleclough, C., Perry, R. P., Karjalainen, K. & Weigert, M. Nature 290, 372–378 (1981).

    Article  ADS  CAS  Google Scholar 

  10. Gathings, W. E., Lawton, A. R. & Cooper, M. D. Eur. J. Immun. 7, 804–810 (1978).

    Article  Google Scholar 

  11. Abney, E. R., Cooper, M. D., Kearney, J. F., Lawton, A. R. & Parkhouse, R. M. E. J. Immun. 120, 2041–2049 (1978).

    CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  16. Vogler, L. B. et al. New Engl. J. Med. 298, 872–878 (1978).

    Article  CAS  Google Scholar 

  17. Vogler, L. B. et al. Nature 290, 339–341 (1981).

    Article  ADS  CAS  Google Scholar 

  18. Burrows, P. D., Beck, G. B. & Wabl, M. R. Proc. natn. Acad. Sci. U.S.A. 78, 564–568 (1981).

    Article  ADS  CAS  Google Scholar 

  19. Alt, F. W., Rosenberg, N., Casanova, R. J., Thomas, E. & Baltimore, D. Nature 296, 325–331 (1982).

    Article  ADS  CAS  Google Scholar 

  20. Lowe, J., Bird, P., Hardie, D., Jefferis, R. & Ling, N. R. Immunology 47, 329–336 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Kubagawa, H., Gathings, W. E., Levitt, D., Kearney, J. F. & Cooper, M. D. J. clin. Immun. 2, 264–269 (1982).

    Article  CAS  Google Scholar 

  22. Mayumi, M., Kuritani, T., Kubagawa, H. & Cooper, M. D. J. Immun. (in the press).

  23. Marcu, K. B. & Cooper, M. D. Nature 298, 327–328 (1982).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  25. Shimizu, A., Takahashi, N., Yaoita, Y. & Honjo, T. Cell 28, 499–506 (1982).

    Article  CAS  Google Scholar 

  26. Mongini, P. K. A., Stein, K. E. & Paul, W. E. J. exp. Med. 153, 1–12 (1981).

    Article  CAS  Google Scholar 

  27. Ellison, J. & Hood, L. Proc. natn. Acad. Sci. U.S.A. 79, 1984–1988 (1982).

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  29. Max, E. E., Battey, J., Ney, R., Kirsch, I. R. & Leder, P. Cell 29, 691–699 (1982).

    Article  CAS  Google Scholar 

  30. Kearney, J.F., Lawton, A. R. & Cooper, M. D. ICN-UCLA Symp. molec. cell. Biol. 6, 313–320 (1977).

    CAS  Google Scholar 

  31. Klein, G. Nature 294, 313–318 (1981).

    Article  ADS  CAS  Google Scholar 

  32. Kubagawa, H., Mayumi, M., Kearney, J. F. & Cooper, M. D. J. exp. Med. 156, 1010–1024 (1982).

    Article  CAS  Google Scholar 

  33. Yaoita, Y., Kumagai, Y., Okumura, K. & Honjo, T. Nature 297, 697–699 (1982).

    Article  ADS  CAS  Google Scholar 

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Authors and Affiliations

  1. The Cellular Immunobiology Unit of the Tumor Institute, Departments of Pediatrics and Microbiology, The Comprehensive Cancer Center, and The Children's Hospital, University of Alabama in Birmingham, Birmingham, Alabama, 35294, USA

    Hiromi Kubagawa, Mitsufumi Mayumi, William M. Crist & Max D. Cooper

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  1. Hiromi Kubagawa
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  2. Mitsufumi Mayumi
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  3. William M. Crist
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  4. Max D. Cooper
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Kubagawa, H., Mayumi, M., Crist, W. et al. Immunoglobulin heavy-chain switching in pre-B leukaemias. Nature 301, 340–342 (1983). https://doi.org/10.1038/301340a0

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  • DOI: https://doi.org/10.1038/301340a0

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