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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cooper, M. D. J. clin. Immun. 1, 81–89 (1981).
Davis, M. M. et al. Nature 283, 733–739 (1980).
Sakano, H., Maki, R., Kurosawa, Y., Roeder, W. & Tonegawa, S. Nature 286, 676–683 (1980).
Maki, R., Kearney, J. F., Paige, C. & Tonegawa, S. Science 209, 1366–1369 (1980).
Perry, R. P., Kelley, D. E., Coleclough, C. & Kearney, J. F. Proc. natn. Acad. Sci. U.S.A. 78, 247–251 (1980).
Alt, F., Rosenberg, N., Lewis, S., Thomas, E. & Baltimore, D. Cell 27, 381–390 (1981).
Korsmeyer, S. J. et al. Proc. natn. Acad. Sci. U.S.A. 78, 7096–7100 (1981).
Hieter, P. A., Korsmeyer, S. J., Waldmann, T. A. & Leder, P. Nature 290, 368–372 (1981).
Coleclough, C., Perry, R. P., Karjalainen, K. & Weigert, M. Nature 290, 372–378 (1981).
Gathings, W. E., Lawton, A. R. & Cooper, M. D. Eur. J. Immun. 7, 804–810 (1978).
Abney, E. R., Cooper, M. D., Kearney, J. F., Lawton, A. R. & Parkhouse, R. M. E. J. Immun. 120, 2041–2049 (1978).
Rabbitts, T. H., Forster, A., Dunnick, W. & Bentley, D. L. Nature 283, 351–356 (1980).
Cory, S., Jackson, J. & Adams, J. M. Nature 285, 450–456 (1980).
Davis, M. M., Kim, S. K. & Hood, L. E. Science 209, 1360–1365 (1980).
Kataoka, T., Miyata, T. & Honjo, T. Cell 23, 357–368 (1981).
Vogler, L. B. et al. New Engl. J. Med. 298, 872–878 (1978).
Vogler, L. B. et al. Nature 290, 339–341 (1981).
Burrows, P. D., Beck, G. B. & Wabl, M. R. Proc. natn. Acad. Sci. U.S.A. 78, 564–568 (1981).
Alt, F. W., Rosenberg, N., Casanova, R. J., Thomas, E. & Baltimore, D. Nature 296, 325–331 (1982).
Lowe, J., Bird, P., Hardie, D., Jefferis, R. & Ling, N. R. Immunology 47, 329–336 (1982).
Kubagawa, H., Gathings, W. E., Levitt, D., Kearney, J. F. & Cooper, M. D. J. clin. Immun. 2, 264–269 (1982).
Mayumi, M., Kuritani, T., Kubagawa, H. & Cooper, M. D. J. Immun. (in the press).
Marcu, K. B. & Cooper, M. D. Nature 298, 327–328 (1982).
Croce, C. M. et al. Proc. natn. Acad. Sci. U.S.A. 76, 3416–3419 (1979).
Shimizu, A., Takahashi, N., Yaoita, Y. & Honjo, T. Cell 28, 499–506 (1982).
Mongini, P. K. A., Stein, K. E. & Paul, W. E. J. exp. Med. 153, 1–12 (1981).
Ellison, J. & Hood, L. Proc. natn. Acad. Sci. U.S.A. 79, 1984–1988 (1982).
Takahashi, N. et al. Cell 29, 671–679 (1982).
Max, E. E., Battey, J., Ney, R., Kirsch, I. R. & Leder, P. Cell 29, 691–699 (1982).
Kearney, J.F., Lawton, A. R. & Cooper, M. D. ICN-UCLA Symp. molec. cell. Biol. 6, 313–320 (1977).
Klein, G. Nature 294, 313–318 (1981).
Kubagawa, H., Mayumi, M., Kearney, J. F. & Cooper, M. D. J. exp. Med. 156, 1010–1024 (1982).
Yaoita, Y., Kumagai, Y., Okumura, K. & Honjo, T. Nature 297, 697–699 (1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/301340a0
This article is cited by
-
Inflammatory and immunological responses in skin and peripheral lymph of sheep following intracutaneous injection ofStaphylococcus aureus
Inflammation (1987)
-
Molecular genetics of immimoglobulin heavy chain switching
Survey of Immunologic Research (1983)
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.