Soluble antigen can cause enhanced apoptosis of germinal-centre B cells

Article metrics

Abstract

GERMINAL centres are dynamic microenvironments of B-lympho-cyte differentiation, which develop in secondary lymphoid tissues during immune responses1-3. Within germinal centres, activated B lymphocytes proliferate and point mutations are rapidly introduced into the genes encoding their immunoglobulin receptors4-10. As a result, new specificities of B cells are created, including those with a heightened capacity to bind the immunizing antigen4-11. Immunoglobulin gene mutation can also lead to reactivity to self antigens12-14. It has been suggested that any newly formed self-reactive B cells are eliminated within the germinal centre in order to avoid autoimmunity15,16. Here we present evidence that antigen-specific, high-affinity, germinal-centre B cells are rapidly killed by apoptosis in situ when they encounter soluble antigen. The effect seems to act directly on the B cells, rather than through helper T cells. Furthermore, the apoptosis is unique to germinal-centre cells, and is only incompletely impeded by constitutive expression of the proto-oncogene bcl-2. This phenomenon may reflect clonal deletion of self-reactive B cells within germinal centres.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    MacLennan, I. C. M. A. Rev. Immun. 12, 117–139 (1994).

  2. 2

    MacLennan, I. C. M., Liu, Y. J., Oldfield, S., Zhang, J. & Lane, P. J. L. Curr. Top. Microbiol. Immun. 159, 138–148 (1990).

  3. 3

    Jacob, J., Kassir, R. & Kelsoe, G. J. exp. Med. 172, 1165–1175 (1991).

  4. 4

    Berek, C., Berger, A. & Apel, M. Cell. 67, 1121–1129 (1991).

  5. 5

    Jacob, J., Kelsoe, G., Rajewsky, K. & Weiss, U. Nature. 354, 389–392 (1991).

  6. 6

    Lalor, P. A., Nossal, G. J. V., Sanderson, R. D. & McHeyzer-Williams, M. G. Eur. J. Immun. 22, 3001–3011 (1992).

  7. 7

    McHeyzer-Williams, M. G., McLean, M. J., Lalor, P. A. & Nossal, G. J. V. J. exp. Med. 178, 295–307 (1993).

  8. 8

    Kuppers, R., Zhao, M., Hansmann, M. L. & Rajewsky, K. EMBO J. 12, 4955–4967 (1993).

  9. 9

    Allen, D. et al. Immun. Rev. 96, 5–22 (1987).

  10. 10

    Allen, D., Simon, T., Sablitzky, F., Rajewsky, K. & Cumano, A. EMBO. J. 7, 1995–2001 (1988).

  11. 11

    Berek, C. & Milstein, C. Immun. Rev. 96, 23–41 (1987).

  12. 12

    Shlomchik, M. J., Marshak-Rothstein, A., Wolfowicz, C. B., Rothstein, T. L. & Weigert, M. G. Nature. 328, 805–811 (1987).

  13. 13

    Shlomchik, M. et al. J. exp. Med. 171, 265–297 (1990).

  14. 14

    Diamond, B. et al. A. Rev. Immun. 10, 737–757 (1992).

  15. 15

    Linton, P.-J., Rudie, A. & Klinman, N. R. J. Immun. 146, 4099–4104 (1991).

  16. 16

    Nossal, G. J. V., Karvelas, M. & Pulendran, B. Proc. natn. Acad. Sci. U.S.A. 90, 3088–3092 (1993).

  17. 17

    Jack, R. S., Imanishi-Kari & Rajewsky, K. Eur. J. Immun. 7, 559–565 (1977).

  18. 18

    Reth, M. G., Hammerling, G. J. & Rajewsky, K. Eur. J. Immun. 8, 393–400 (1978).

  19. 19

    Herzenberg, L. A., Black, S. J., Tokuhisha, T. & Herzenberg, L. A. J. exp. Med. 151, 1071–1087 (1980).

  20. 20

    Gavrieli, Y., Sherman, Y. & Ben-Sasson, S. A. J. Cell. Biol. 119, 493–501 (1992).

  21. 21

    Theofilopoulos, A. N. & Dixon, F. J. Adv. Immun. 28, 89–220 (1978).

  22. 22

    Vaux, D. L. Proc. natn. Acad. Sci. U.S.A. 90, 786–789 (1993).

  23. 23

    Nakayama, K.-i. et al. Science. 261, 1548–1588 (1993).

  24. 24

    Veis, D. J., Sorenson, C. M., Shutter, J. R. & Korsmeyer, S. J. Cell. 75, 229–240 (1993).

  25. 25

    Hartley, S. B. et al. Cell. 72, 325–335 (1993).

  26. 26

    Nisitani, S., Tsubata, T., Murakami, M., Okamoto, M. & Honjo, T. J. exp. Med. 178, 1247–1254 (1993).

  27. 27

    Hockenbery, D. M., Zutter, M., Hickey, W., Nahm, M. & Korsmeyer, S. J. Proc. natn. Acad. Sci. U.S.A. 88, 6961–6965 (1991).

  28. 28

    Liu, Y. J. et al. Eur. J. Immun. 21, 1905–1910 (1991).

  29. 29

    Smith, K. G. C., Weiss, U., Rajewsky, K., Nossal, G. J. V. & Tarlinton, D. M. Immunity. 1, 803–813 (1994).

  30. 30

    Strasser, A. et al. Proc. natn. Acad. Sci. U.S.A. 88, 8661–8665 (1991).

  31. 31

    Shokat, K. M. & Goodnow, C. C. Nature 375, 334–338 (1995).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Pulendran, B., Kannourakis, G., Nouri, S. et al. Soluble antigen can cause enhanced apoptosis of germinal-centre B cells. Nature 375, 331–334 (1995) doi:10.1038/375331a0

Download citation

Further reading

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.