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B-cell-specif ic coactivator OBF-1/OCA-B/Bob1 required for immune response and germinal centre formation

Abstract

THE B-lymphocyte-specific transcriptional factor called Oct binding factor (OBF)-1, OCA-B or Bob1 (refs 1–3) is thought to be involved in the transcription of immunoglobulin genes through recruitment to the highly conserved octamer site of immunoglobulin promoters, mediated by either Oct-1 or Oct-2. To define the in vivo role of OBF-1 we have used gene targeting in embryonic stem cells to generate mice lacking the coactivator OBF-1. Such OBF-1−/− mice are born normally, are fertile and seem healthy, and surprisingly, rearrangement and transcription of immunoglobulin genes are largely unaffected. However, mice deficient in OBF-1 have reduced numbers of mature B cells and a severe reduction in the number of recirculating B cells, but otherwise show normal B-cell differentiation. Serum IgA and particularly IgG levels are greatly reduced. If mutant mice are immunized with either a thymus-independent or a thymus-dependent antigen, their immune responses are dramatically weakened. Strikingly, germinal centres completely fail to develop after immunization with thymus-dependent antigen. Our results demonstrate that in vivo OBF-1 is not required for initial transcription of immunoglobulin genes or for B cell development, but instead is essential for the response of B cells to antigens, and is required for the formation of germinal centres.

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References

  1. Strubin, M., Newell, J. W. & Matthias, P. Cell 80, 497–506 (1995).

    Article  CAS  Google Scholar 

  2. Gstaiger, M., Knoepfel, L., Georgiev, O., Schaffner, W. & Hovens, C. M. Nature 373, 360–362 (1995).

    Article  ADS  CAS  Google Scholar 

  3. Luo, Y. & Roeder, R. G. Mol. Cell. Biol. 15, 4115–4124 (1995).

    Article  CAS  Google Scholar 

  4. Staudt, L. M. & Lenardo, M. J. Annu. Rev. Immunol. 9, 373–398 (1991).

    Article  CAS  Google Scholar 

  5. Mizushima-Sugano, J. & Roeder, R. G. Proc. Natl Acad. Sci. USA 83, 8511–8515 (1986).

    Article  ADS  CAS  Google Scholar 

  6. Mason, J. O., Williams, G. T. & Neuberger, M. S. Cell 41, 479–487 (1985).

    Article  CAS  Google Scholar 

  7. Dreyfus, M., Doyen, N. & Rougeon, F. EMBO J. 6, 1685–1690 (1987).

    Article  CAS  Google Scholar 

  8. Wirth, T., Staudt, L. & Baltimore, D. Nature 329, 174–177 (1987).

    Article  ADS  CAS  Google Scholar 

  9. Jenuwein, T. & Grosschedl, R. Genes Dev. 5, 932–943 (1991).

    Article  CAS  Google Scholar 

  10. Sturm, R. A., Das, G. & Herr, W. Genes Dev. 2, 1582–1599 (1988).

    Article  CAS  Google Scholar 

  11. Staudt, L. M. et al. Nature 323, 640–643 (1986).

    Article  ADS  CAS  Google Scholar 

  12. Müller, M. M., Ruppert, S., Schaffner, W. & Matthias, P. Nature 336, 544–551 (1988).

    Article  ADS  Google Scholar 

  13. Clerc, R. G., Corcoran, L. M., LeBowitz, J. H., Baltimore, D. & Sharp, P. A. Genes Dev. 2, 1570–1581 (1988).

    Article  CAS  Google Scholar 

  14. Scheidereit, C. et al. Nature 336, 551–557 (1988).

    Article  ADS  CAS  Google Scholar 

  15. Corcoran, L. et al. Genes Dev. 7, 570–582 (1993).

    Article  CAS  Google Scholar 

  16. Corcoran, L. M. & Karvelas, M. Immunity 1, 635–645 (1994).

    Article  CAS  Google Scholar 

  17. Feldhaus, A. L., Klug, C. A., Arvin, K. L. & Singh, H. EMBO J. 12, 2763–2772 (1993).

    Article  CAS  Google Scholar 

  18. Pfisterer, P., Annweiler, A., Ullmer, C., Corcoran, L. M. & Wirth, T. EMBO J. 13, 1655–1663 (1994).

    Article  Google Scholar 

  19. Luo, Y., Fujii, H., Gerster, T. & Roeder, R. G. Cell 71, 231–241 (1992).

    Article  CAS  Google Scholar 

  20. Schubart, D. B. et al. Nucleic Acids Res. 24, 1913–1920 (1996).

    Article  ADS  CAS  Google Scholar 

  21. Rolink, A. et al. Immunologist 3, 125–128 (1995).

    CAS  Google Scholar 

  22. Rolink, A., Grawunder, U., Winkler, T. H., Karasuyama, H. & Melchers, F. Int. Immunol. 6, 1257–1264 (1994).

    Article  CAS  Google Scholar 

  23. Ahmed, R. & Gray, D. Science 272, 54–60 (1996).

    Article  ADS  CAS  Google Scholar 

  24. Kelsoe, G. Immunity 4, 107–111 (1996).

    Article  CAS  Google Scholar 

  25. Humphrey, J. H., Grennan, D. & Sundaram, V. Eur. J. Immunol. 14, 859–864 (1984).

    Article  CAS  Google Scholar 

  26. Castigli, E. et al. Proc. Natl Acad. Sci. USA 91, 12135–12139 (1994).

    Article  ADS  CAS  Google Scholar 

  27. Xu, J. et al. Immunity 1, 423–431 (1994).

    Article  CAS  Google Scholar 

  28. Hibbs, M. L. et al. Cell 83, 301–311 (1995).

    Article  CAS  Google Scholar 

  29. Stief, A. et al. J. Immunol. 152, 3378–3390 (1994).

    CAS  PubMed  Google Scholar 

  30. Wood, S. A. et al. Proc. Natl Acad. Sci. USA 90, 4582–4585 (1993).

    Article  ADS  CAS  Google Scholar 

Download references

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Schubart, D., Rolink, A., Kosco-Vilbois, M. et al. B-cell-specif ic coactivator OBF-1/OCA-B/Bob1 required for immune response and germinal centre formation. Nature 383, 538–542 (1996). https://doi.org/10.1038/383538a0

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