A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production (2025)

  • 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 VHDJH 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

Access through your institution

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

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

A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production (1)

The immunoglobulin heavy chain super enhancer controls class switch recombination in developing B cells

Article Open access 28 March 2024

A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production (2)

Dynamics of heavy chain junctional length biases in antibody repertoires

Article Open access 01 May 2020

A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production (3)

Reprogramming human B cells with custom heavy-chain antibodies

Article 22 July 2024

References

  1. Tonegawa, S. Nature 302, 575–581 (1983).

    Article ADS CAS Google Scholar

  2. Yancopoulos, G. D. & Alt, F. W. A. Rev. Immun. 4, 339–368 (1986).

    Article CAS Google Scholar

  3. Alt, F. W. et al. EMBO J. 3, 1209–1219 (1984).

    Article CAS Google Scholar

  4. Sakano, H., Maki, R., Kurosawa, Y., Roeder, W. & Tonegawa, S. Nature 286, 676–683 (1980).

    Article ADS CAS Google Scholar

  5. Alt, F. W. & Baltimore, D. Proc. natn. Acad. Sci. U.S.A. 79, 4118–4122 (1982).

    Article ADS CAS Google Scholar

  6. Steinmetz, M., Altenburger, W. & Zachau, H. G. Nucleic Acids Res. 8, 709–1720 (1980).

    Google Scholar

  7. Hagiya, M. et al. Proc. natn. Acad. Sci. U.S.A. 83, 145–149 (1986).

    Article ADS CAS Google Scholar

  8. Reth, M. G. & Alt, F. W. Nature 312, 418–423 (1984).

    Article ADS CAS Google Scholar

  9. Reth, M. G., Jackson, S. & Alt, F. W. EMBO J. (in the press).

  10. Reth, M. G., Ammirati, P., Jackson, S. & Alt, F. Nature 317, 353–355 (1985).

    Article ADS CAS Google Scholar

  11. Alt, F. W., Blackwell, T. K., DePinho, R. A., Reth, M. G. & Yancopoulos, G. D. Immun. Rev. 89, 5–20 (1986).

    Article CAS Google Scholar

  12. Rosenberg, N. & Baltimore, D. J. exp. Med. 143, 1453–1463 (1976).

    Article CAS Google Scholar

  13. Brodeur, P. & Riblet, R. Eur. J. Immun. 14, 922–930 (1984).

    Article CAS Google Scholar

  14. Brodeur, P. & Riblet, R. UCLA Symp. molec. cell. Biol. new Ser. 18, 445 (1984).

    CAS Google Scholar

  15. Dildrop, R. Immun. Today 5, 85–86 (1984).

    Article CAS Google Scholar

  16. 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

  17. Early, P., Nottenburg, C., Weissman, I. & Hood, L. Molec. cell. Biol. 2, 829–831 (1982).

    Article CAS Google Scholar

  18. Hochtl, J. & Zachau, H. G. Nature 302, 260–263 (1983).

    Article ADS CAS Google Scholar

  19. 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

  20. Siminovitch, K. A., Bakhski, A., Goldman, P. & Korsmeyer, S. J. Nature 316, 260–263 (1985).

    Article ADS CAS Google Scholar

  21. 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

  22. Van Ness, B. G. et al. Cell 27, 593–602 (1981).

    Article CAS Google Scholar

  23. Picard, D. & Schaffner, W. EMBO J. 3, 3031–3039 (1984).

    Article CAS Google Scholar

  24. Yancopoulos, G. D. & Alt, F. W. Cell 40, 271–281 (1985).

    Article CAS Google Scholar

  25. Blackwell, T. K., Yancopoulos, G. D. & Alt, F. W. UCLA Symp. molec. cell. Biol., new Ser. 19, 537 (1984).

    CAS Google Scholar

  26. Siu, G. et al. Nature 311, 344–350 (1984).

    Article ADS CAS Google Scholar

  27. Wang, X. F. & Calame, K. Cell 43, 659–665 (1985).

    Article CAS Google Scholar

  28. Gillies, S. D., Morrison, S. L., Oi, V. T. & Tonegawa, S. Cell 33, 717–728 (1983).

    Article CAS Google Scholar

  29. Banerji, J., Olson, L. & Schaffner, W. Cell 33, 729–740 (1983).

    Article CAS Google Scholar

  30. Neuberger, M. S. EMBO J. 2, 1373–1378 (1983).

    Article CAS Google Scholar

  31. Yancopoulos, G. D., Blackwell, T. K., Suh, H., Hood, L. & Alt, F. W. Cell 44, 251–259 (1986).

    Article CAS Google Scholar

  32. 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).

  33. Barth, R. K. et al. Nature 316, 518–523 (1985).

    Article ADS Google Scholar

  34. Arden, B., Klotz, J., Siu, G. & Hood, L. Nature 316, 518–523 (1985).

    Article Google Scholar

  35. Becker, D. et al. Nature 317, 430–434 (1985).

    Article ADS CAS Google Scholar

  36. Kranz, D. M. et al. Nature 313, 752–755 (1985).

    Article ADS CAS Google Scholar

  37. Hayday, A. C. et al. Cell 40, 259–269 (1985).

    Article CAS Google Scholar

  38. Lefranc, M. P., Forster, A. & Rabbitts, T. H. Nature 319, 420–422 (1986).

    Article ADS CAS Google Scholar

  39. Lewis, S., Rosenberg, N., Alt, F. & Baltimore, D. Cell 30, 807–816 (1982).

    Article CAS Google Scholar

  40. Feddersen, R. M. & Van Ness, B. G. Proc. natn. Acad. Sci. U.S.A. 82, 4793–4797 (1985).

    Article ADS CAS Google Scholar

  41. Yancopoulos, G. D. et al. Nature 311, 727–733 (1984).

    Article ADS CAS Google Scholar

  42. De Wet et al. J. Virol. 33, 401–410 (1980).

    CAS PubMed PubMed Central Google Scholar

  43. Maxam, A. & Gilbert, W. Meth. Enzym. 65, 419–460 (1980).

    Google Scholar

Download references

Author information

Authors and Affiliations

  1. Institute for Genetics, University of Cologne, Weyertal 121, D-5000, Köln, 41, FRG

    Michael Reth,Peter Gehrmann,Eva Petrac&Petra Wiese

Authors

  1. Michael Reth

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  2. Peter Gehrmann

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  3. Eva Petrac

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  4. 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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/322840a0

This article is cited by

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.

A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production (2025)
Top Articles
Latest Posts
Recommended Articles
Article information

Author: Carlyn Walter

Last Updated:

Views: 6204

Rating: 5 / 5 (50 voted)

Reviews: 81% of readers found this page helpful

Author information

Name: Carlyn Walter

Birthday: 1996-01-03

Address: Suite 452 40815 Denyse Extensions, Sengermouth, OR 42374

Phone: +8501809515404

Job: Manufacturing Technician

Hobby: Table tennis, Archery, Vacation, Metal detecting, Yo-yoing, Crocheting, Creative writing

Introduction: My name is Carlyn Walter, I am a lively, glamorous, healthy, clean, powerful, calm, combative person who loves writing and wants to share my knowledge and understanding with you.