Nature 280, 288 - 294 (26 July 1979); doi:10.1038/280288a0

Sequences at the somatic recombination sites of immunoglobulin light-chain genes

Hitoshi Sakano, Konrad Hüppi, Günther Heinrich & Susumu Tonegawa

Basel Institute for Immunology, 487 Grenzacherstrasse, Postfach, CH-4005 Basel, Switzerland

The entire nucleotide sequence of a 1.7-kilobase embryonic DNA fragment containing five joining (J) DNA segments for mouse immunoglobulin chain gene has been determined. Each J DNA segment can encode amino acid residues 96−108. Comparison of one of the five J DNA sequences with those of an embryonic variable (V) gene and a complete chain gene permitted localisation of a precise recombination site. The 5'-flanking regions of J DNA segments could form an inverted stem structure with the 3'-non-coding region of embryonic V genes. This hypothetical structure and gel-blotting analysis of total embryo and myeloma DNA suggest that the somatic recombination may be accompanied by excision of an entire DNA segment between a V gene and a J DNA segment. Antibody diversity may in part be generated by modulation of the precise recombination sites.

References

1.	Hozumi, N. & Tonegawa, S. Proc. natn. Acad. Sci. U.S.A. 73, 3628–3632 (1976).
2.	Tonegawa, S., Hozumi, N., Matthyssens, G. & Schuller, R. Cold Spring Harb. Symp. quant. Biol. 41, 877–889 (1976).
3.	Brack, C., Hirama, M., Schuller, R. & Tonegawa, S. Cell 15, 1–14 (1978).
4.	Bernard, O., Hozumi, N. & Tonegawa, S. Cell 15, 1133–1144 (1978).
5.	Tonegawa, S., Maxam, A. M., Tizard, R., Bernard, O. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 3171–3175 (1978).
6.	Klessing, D. F. Cell 12, 9–21 (1977).
7.	Berget, S. M., Moore, C. & Sharp, P. A. Proc. natn. Acad. Sci. U.S.A. 74, 3171–3175 (1977).
8.	Lenhard-Schuller, R., Hohn, B., Brack, C., Hirama, M. & Tonegawa, S. Proc. natn. Acad. Sci. U.S.A. 74, 4709–4713 (1978).
9.	Brack, C. et al. (in preparation).
10.	McKean, D. J., Bell, M. & Potter, M. Proc. natn. Acad. Sci. U.S.A. 75, 3913–3917 (1978).
11.	Weigert, M., Gatmaitan, L., Loh, E., Schilling, J. & Hood, L. Nature 276, 785–790 (1978).
12.	Breathnach, R., Benoist, C., O'Hare, K., Cannon, F. & Chambon, P. Proc. natn. Acad. Sci. U.S.A. 75, 4853–4857 (1978).
13.	Seidman, J. G. et al. Proc. natn. Acad. Sci. U.S.A. 75, 3881–3885 (1978).
14.	Ohtsubo, H. & Ohtsubo, E. Proc. natn. Acad. Sci. U.S.A. 75, 615–619 (1978).
15.	Grindley, N. D. F. Cell 13, 419–426 (1978).
16.	Ohtsubo, H., Ohmori, H. & Ohtsubo, E. Cold Spring Harb. Symp. quant. Biol. 43 (in the press).
17.	Calos, M. P., Johnarud, L. & Miller, J. H. Cell 13, 411–418 (1978).
18.	Allet, B. Cell 16, 123–129 (1979).
19.	Oka, A., Nomura, N., Sugimoto, K., Sugisaki, H. & Takanami, M. Nature 276, 845–847 (1978).
20.	Rosenberg, M., Court, D., Shimatake, H., Brady, C. & Wulff, D. L. Nature 272, 414–422 (1978).
21.	Johnsrud, L., Calos, M. P. & Miller, J. H. Cell 15, 1209–1219 (1978).
22.	Ghosal, D., Sommer, H. & Saedler, H. Nucleic Acids Res. 6, 1111–1122 (1979).
23.	Hill, R. L., Delaney, R., Fellow, R. E. & Lebovitz, H. E. Proc. natn. Acad. Sci. U.S.A. 63, 1762–1768 (1966).
24.	Edelman, G. M. et al. Proc. natn. Acad. Sci. U.S.A. 63, 78–85 (1969).
25.	Poljak, R. J. et al. Proc. natn. Acad. Sci. U.S.A. 70, 3305–3310 (1973).
26.	Sakano, H. et al. Nature 277, 627–633 (1979).
27.	Weigert, M. & Riblet, R. Cold Spring Harb. Symp. quant. Biol. 41, 837–846 (1976).
28.	Valbuena, O., Marcu, K. B., Weigert, M. & Perry, R. P. Nature 276, 780–784 (1978).
29.	Wu, T. T. & Kabat, E. A. J. exp. Med. 132, 211–250 (1970).
30.	Tiemeier, D., Enquist, L. & Leder, P. Nature 263, 526–527 (1976).
31.	Smith, H. O. & Birnstiel, M. L. Nucleic Acids Res. 3, 2387–2398 (1976).
32.	Boliver, E. et al. Gene 2, 582–564 (1978).
33.	Maxam, A. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 560–564 (1978).
34.	Klenow, H., Hansen, K. & Patkar, S. A. Eur. J. Biochem. 22, 371–381 (1971).
35.	Hill, R. L., Belamey, R., Fellows, R. E. & Lavovitz, H. E. Proc. natn. Acad. Sci. U.S.A. 56, 1762–1768 (1966).
36.	Kleckner, N. Cell 16, 711–720 (1979).