Abstract
During B-cell development, theVH genes of immunoglobulin heavy (H) chains are assembled from three different germline components: the variable (VH) segment, the diversity (D) segment and the joining (JH) segment1,2. The joining between two segments involves the recognition of conserved nonamer–heptamer sequences bordering each segment, double-stranded cuts at the heptamer–segment border, and the re-ligation of the two segment ends which have frequently been modified by the deletion and addition of nucleotides3–6. The flexibility of the joint increases VHDJHvariability. However, it also results in many pre-B cells which do not produce immunoglobulin H chains and have non-functional VHDJH complexes carrying the VH and JH coding sequences in different reading frames7. We show here that such ‘null cells’ are not dead-end products of the B-cell developmental pathway but can perform a novel VH to VHDJH joining using a 5′ VH segment to replace the VH sequence of the VHDJ−H complex. This process can result in the generation of a VHDJ+H complex and the subsequent expression of an immunoglobulin heavy chain.
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References
Tonegawa, S. Nature 302, 575–581 (1983).
Yancopoulos, G. D. & Alt, F. W. A. Rev. Immun. 4, 339–368 (1986).
Alt, F. W. et al. EMBO J. 3, 1209–1219 (1984).
Sakano, H., Maki, R., Kurosawa, Y., Roeder, W. & Tonegawa, S. Nature 286, 676–683 (1980).
Alt, F. W. & Baltimore, D. Proc. natn. Acad. Sci. U.S.A. 79, 4118–4122 (1982).
Steinmetz, M., Altenburger, W. & Zachau, H. G. Nucleic Acids Res. 8, 709–1720 (1980).
Hagiya, M. et al. Proc. natn. Acad. Sci. U.S.A. 83, 145–149 (1986).
Reth, M. G. & Alt, F. W. Nature 312, 418–423 (1984).
Reth, M. G., Jackson, S. & Alt, F. W. EMBO J. (in the press).
Reth, M. G., Ammirati, P., Jackson, S. & Alt, F. Nature 317, 353–355 (1985).
Alt, F. W., Blackwell, T. K., DePinho, R. A., Reth, M. G. & Yancopoulos, G. D. Immun. Rev. 89, 5–20 (1986).
Rosenberg, N. & Baltimore, D. J. exp. Med. 143, 1453–1463 (1976).
Brodeur, P. & Riblet, R. Eur. J. Immun. 14, 922–930 (1984).
Brodeur, P. & Riblet, R. UCLA Symp. molec. cell. Biol. new Ser. 18, 445 (1984).
Dildrop, R. Immun. Today 5, 85–86 (1984).
Krawinkel, U., Zoebelein, G., Brüggemann, M., Radbruch, A. & Rajewsky, K. Proc. natn. Acad. Sci U.S.A. 80, 4997–5001 (1983).
Early, P., Nottenburg, C., Weissman, I. & Hood, L. Molec. cell. Biol. 2, 829–831 (1982).
Hochtl, J. & Zachau, H. G. Nature 302, 260–263 (1983).
Moore, M. W., Durdik, J., Persiani, D. M. & Selsing, E. Proc. natn. Acad. Sci. U.S.A. 82, 6211–6215 (1985).
Siminovitch, K. A., Bakhski, A., Goldman, P. & Korsmeyer, S. J. Nature 316, 260–263 (1985).
Kemp, D. J., Harris, A. W., Cory, S. & Adams, J. M. Proc. natn. Acad. Sci. U.S.A. 77, 2876–2880 (1980).
Van Ness, B. G. et al. Cell 27, 593–602 (1981).
Picard, D. & Schaffner, W. EMBO J. 3, 3031–3039 (1984).
Yancopoulos, G. D. & Alt, F. W. Cell 40, 271–281 (1985).
Blackwell, T. K., Yancopoulos, G. D. & Alt, F. W. UCLA Symp. molec. cell. Biol., new Ser. 19, 537 (1984).
Siu, G. et al. Nature 311, 344–350 (1984).
Wang, X. F. & Calame, K. Cell 43, 659–665 (1985).
Gillies, S. D., Morrison, S. L., Oi, V. T. & Tonegawa, S. Cell 33, 717–728 (1983).
Banerji, J., Olson, L. & Schaffner, W. Cell 33, 729–740 (1983).
Neuberger, M. S. EMBO J. 2, 1373–1378 (1983).
Yancopoulos, G. D., Blackwell, T. K., Suh, H., Hood, L. & Alt, F. W. Cell 44, 251–259 (1986).
Kabat, E. A., Wu, T. T., Bilofsky, H., Reid-Miller, M. & Perry, H. (eds) Sequences of Proteins of Biological Interest No. 80–2008 (NIH, Bethesda, 1983).
Barth, R. K. et al. Nature 316, 518–523 (1985).
Arden, B., Klotz, J., Siu, G. & Hood, L. Nature 316, 518–523 (1985).
Becker, D. et al. Nature 317, 430–434 (1985).
Kranz, D. M. et al. Nature 313, 752–755 (1985).
Hayday, A. C. et al. Cell 40, 259–269 (1985).
Lefranc, M. P., Forster, A. & Rabbitts, T. H. Nature 319, 420–422 (1986).
Lewis, S., Rosenberg, N., Alt, F. & Baltimore, D. Cell 30, 807–816 (1982).
Feddersen, R. M. & Van Ness, B. G. Proc. natn. Acad. Sci. U.S.A. 82, 4793–4797 (1985).
Yancopoulos, G. D. et al. Nature 311, 727–733 (1984).
De Wet et al. J. Virol. 33, 401–410 (1980).
Maxam, A. & Gilbert, W. Meth. Enzym. 65, 419–460 (1980).
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Reth, M., Gehrmann, P., Petrac, E. et al. A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production. Nature 322, 840–842 (1986). https://doi.org/10.1038/322840a0
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DOI: https://doi.org/10.1038/322840a0
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