Abstract
Human immunoglobulin light-chain genes become rearranged in an ordered fashion during pre-B-cell development such that rearrangement generally occurs in κ genes before λ genes (refs 1,2). This ordered process includes an unanticipated deletion of the constant κ (Cκ) gene and κ enhancer sequence which precedes λ rearrangement1–4, and the site of this deletional recombination was located 3′ to the joining ( Jκ) segments in 75% of cases studied. We have now characterized the recombinational element responsible for this event on three separate alleles and found them to be identical. This κ-deleting element recombined site-specifically with a palindromic signal (CACAGTG) located in the Jκ–Cκ intron. All losses of Cκ genes in other human B cells were mediated by this determinant, including the 25% of instances when this element recombined with sequences 5′ to Jκ. In contrast, the κ-deleting element remained in its germline form on all successful κ-producing alleles. Moreover, κ loss is an evolutionary conserved event, as the κ-deleting element appears to be the human homologue of the murine RS sequence5. Our results suggest that this element may help ensure isotypic and allelic exclusion of light chains and may be involved in the ordered use of human light-chain genes.
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
Korsmeyer, S. J. et al. Proc. natn. Acad. Sci. U.S.A. 78, 7096–7100 (1981).
Korsmeyer, S. J. et al. J. clin. Invest. 71, 301–313 (1983).
Hieter, P. A., Korsmeyer, S. J., Waldmann, T. A. & Leder, P. Nature 290, 368–372 (1981).
Nadler, L. M. et al. J. clin. Invest. 74, 332–340 (1984).
Durdik, J., Moore, M. W. & Selsing, E. Nature 307, 749–752 (1984).
Korsmeyer, S. J. et al. J. exp. Med. 156, 975–985 (1982).
Brack, C., Hirama, M., Lenhard-Schuller, R. & Tonegawa, S. Cell 15, 1–14 (1978).
Seidman, J. G. & Leder, P. Nature 276, 790–795 (1978).
Max, E. E., Seidman, J. G. & Leder, P. Proc. natn. Acad. Sci. U.S.A. 76, 3450–3454 (1979).
Sakano, H., Huppi, K., Heinrich, G. & Tonegawa, S. Nature 280, 288–294 (1979).
Early, P., Huang, H., Davis, M., Calame, K. & Hood, L. Cell 19, 981–992 (1980).
Alt, F. W., Enea, V., Bothwell, A. L. M. & Baltimore, D. Cell 21, 1–12 (1980).
Coleclough C., Perry, R. P., Karjalainen, K. & Weigert, M. Nature 290, 372–378 (1981).
Lewis, S., Rosenberg, N., Alt, F. & Baltimore, D. Cell 30, 807–816 (1982).
Choi, C., Kuehl, M. & Wall, R. Nature 286, 776–779 (1980).
Seidman, J. G. & Leder, P. Nature 286, 779–783 (1980).
Emorine, L., Kuehl, M., Weir, L., Leder, P. & Max, E. E. Nature 304, 447–449 (1983).
Queen, C. & Baltimore, D. Cell 33, 741–748 (1983).
Scholer, H. R. & Gruss, P. Cell 36, 403–411 (1984).
Mercola, M., Goverman, J., Mirell, C. & Calame, K. Science 227, 266–270 (1985).
Ephrussi, A., Church, G. M., Tonegawa, S. & Gilbert, W. Science 227, 134–140 (1985).
Stong, R. C., Korsmeyer, S. J., Parkin, J. L., Arthur, D. C. & Kersey, J. H. Blood 65, 21–31 (1985).
Winter, J. N., Variakojis, D. & Epstein, A. L. Blood 63, 140–146 (1984).
Minowada, J. in Leukemia (eds Gunz, F. & Henderson, E.) 119–139 (Grune & Stratum, New York. 1982).
Polsky, F. M., Edgel, M. H., Seidman, J. G. & Leder, P. Analyt. Biochem. 87, 397–410 (1978).
Alwine, J. C. et al. Meth. Enzym. 68, 220–242 (1980).
Rigby, D. J., Dieckman, M., Rhodes, C. & Berg, P. J. molec. Biol. 113, 237–251 (1977).
Lenoir, G. M., Preud'homme, J. L., Bernheim, A. & Berger, R. Nature 298, 474–476 (1982).
Hieter, P. A., Maizel, J. V. Jr & Leder, P. J. biol. Chem. 257, 1516–1522 (1982).
Sanger, F., Nicklen, S. & Coulsen, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
Grunstein, M. & Hogness, D. Proc. natn. Acad. Sci. U.S.A. 72, 3961–3965 (1975).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Siminovitch, K., Bakhshi, A., Goldman, P. et al. A uniform deleting element mediates the loss of κ genes in human B cells. Nature 316, 260–262 (1985). https://doi.org/10.1038/316260a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/316260a0
This article is cited by
-
Next-generation sequencing for MRD monitoring in B-lineage malignancies: from bench to bedside
Experimental Hematology & Oncology (2022)
-
IgCaller for reconstructing immunoglobulin gene rearrangements and oncogenic translocations from whole-genome sequencing in lymphoid neoplasms
Nature Communications (2020)
-
Laboratory Diagnosis of Primary Immunodeficiencies
Clinical Reviews in Allergy & Immunology (2014)
-
Use of V(D)J recombination excision circles to identify T- and B-cell defects and to monitor the treatment in primary and acquired immunodeficiencies
Journal of Translational Medicine (2013)
-
Evolution of the porcine (Sus scrofa domestica) immunoglobulin kappa locus through germline gene conversion
Immunogenetics (2012)
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.