- Letter
- Published:
- Michael Reth1,
- Peter Gehrmann1,
- Eva Petrac1 &
- …
- Petra Wiese1
Nature volume322,pages 840–842 (1986)Cite this article
-
326 Accesses
-
321 Citations
-
Metrics details
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.
This is a preview of subscription content, access via your institution
Access options
Change institution
Buy or subscribe
Subscribe to this journal
Receive 51 print issues and online access
185,98€ per year
only 3,65 € per issue
Learn more
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
The immunoglobulin heavy chain super enhancer controls class switch recombination in developing B cells
Article Open access 28 March 2024
Dynamics of heavy chain junctional length biases in antibody repertoires
Article Open access 01 May 2020
Reprogramming human B cells with custom heavy-chain antibodies
Article 22 July 2024
References
Tonegawa, S. Nature 302, 575–581 (1983).
Article ADS CAS Google Scholar
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).
Article ADS CAS Google Scholar
Alt, F. W. & Baltimore, D. Proc. natn. Acad. Sci. U.S.A. 79, 4118–4122 (1982).
Article ADS CAS Google Scholar
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).
Article ADS CAS Google Scholar
Reth, M. G. & Alt, F. W. Nature 312, 418–423 (1984).
Article ADS CAS Google Scholar
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).
Article ADS CAS Google Scholar
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).
CAS Google Scholar
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).
Article ADS CAS Google Scholar
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).
Article ADS CAS Google Scholar
Moore, M. W., Durdik, J., Persiani, D. M. & Selsing, E. Proc. natn. Acad. Sci. U.S.A. 82, 6211–6215 (1985).
Article ADS CAS Google Scholar
Siminovitch, K. A., Bakhski, A., Goldman, P. & Korsmeyer, S. J. Nature 316, 260–263 (1985).
Article ADS CAS Google Scholar
Kemp, D. J., Harris, A. W., Cory, S. & Adams, J. M. Proc. natn. Acad. Sci. U.S.A. 77, 2876–2880 (1980).
Article ADS CAS Google Scholar
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).
CAS Google Scholar
Siu, G. et al. Nature 311, 344–350 (1984).
Article ADS CAS Google Scholar
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).
Article ADS CAS Google Scholar
Kranz, D. M. et al. Nature 313, 752–755 (1985).
Article ADS CAS Google Scholar
Hayday, A. C. et al. Cell 40, 259–269 (1985).
Lefranc, M. P., Forster, A. & Rabbitts, T. H. Nature 319, 420–422 (1986).
Article ADS CAS Google Scholar
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).
Article ADS CAS Google Scholar
Yancopoulos, G. D. et al. Nature 311, 727–733 (1984).
Article ADS CAS Google Scholar
De Wet et al. J. Virol. 33, 401–410 (1980).
Maxam, A. & Gilbert, W. Meth. Enzym. 65, 419–460 (1980).
Author information
Authors and Affiliations
Institute for Genetics, University of Cologne, Weyertal 121, D-5000, Köln, 41, FRG
Michael Reth,Peter Gehrmann,Eva Petrac&Petra Wiese
Authors
- Michael Reth
View author publications
You can also search for this author in PubMedGoogle Scholar
- Peter Gehrmann
View author publications
You can also search for this author in PubMedGoogle Scholar
- Eva Petrac
View author publications
You can also search for this author in PubMedGoogle Scholar
- Petra Wiese
View author publications
You can also search for this author in PubMedGoogle Scholar
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/322840a0
This article is cited by
-
Conserved cryptic recombination signals in Vκ gene segments are cleaved in small pre-B cells
- Anne E Lieberman
- Masayuki Kuraoka
- Lindsay G Cowell
BMC Immunology (2009)
-
Receptor editing in lymphocyte development and central tolerance
- David Nemazee
Nature Reviews Immunology (2006)
-
Gene conversion in human rearranged immunoglobulin genes
- John M. Darlow
- David I. Stott
Immunogenetics (2006)
-
Diversification of the Ig Variable Region Gene Repertoire of Synovial B Lymphocytes by Nucleotide Insertion and Deletion
- Yasushi Miura
- Charles C. Chu
- Nicholas Chiorazzi
Molecular Medicine (2003)
-
Role of antigen receptor affinity in T cell–independent antibody responses in vivo
- Tien-An Yang Shih
- Mario Roederer
- Michel C. Nussenzweig
Nature Immunology (2002)
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.