Abstract
Polyclonal activation has been proposed as the reason that auto-antibodies are produced during autoimmune disease1–3. This model denies a role for specific antigen selection of B cells and predicts instead a multiclonal population of unmutated or randomly mutated autoantibodies. We have found that the genetic features and clonal composition of spontaneously derived immunoglobulin G (IgG) antiself-IgG (rheumatoid factor (RF)) autoantibodies derived from the autoimmune MRL/lpr mouse strain are inconsistent with both the predictions of this model and the actual outcome of experimental polyclonal activation4,5. Instead we have found that MRL/lpr RFs are oligoclonal or even monoclonal in origin. They harbour numerous somatic mutations which are distributed in a way that suggests immunoglobulin-receptor-depen-dent selection of these mutations. In this sense, the MRL/lpr RFs resemble antibodies elicited by exogenous antigens after secondary immunization6–8. The parallels suggest that, like secondary immune responses, antigen stimulation is important in the generation of MRL/lpr RFs.
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References
1. Hang, L. et al. J. exp. Med. 157, 874–883 (1983). 2. Dziarski, R. J. Immun. 128, 1018–1025 (1982). 3. Teodorescu, M. Immun. Rev. 55, 155–178 (1981). 4. Shlomchik, M. J. et al. J. exp. Med. 164, 407–427 (1986). 5. Shlomchik, M. J., Nemazee, D. A., Van Snick, J. & Weigert, M. G. J. exp. Med. 165,970–987 (1987). 6. Clarke, S. H. et al. J. exp. Med. 161, 687–704 (1985). 7. Caton, A. J., Brownlee, G. G., Staudt, L. M. & Gerhard, W. EMBOJ. 5, 1577–1587 (1986). 8. Siekevitz, M., Kocks, C., Rajewsky, K. & Dildrop, R. Cell 48, 757–770 (1987). 9. Izui, S. et al. J. Immun. 133, 227–233 (1984). 10. Theofilopoulos, A. N. & Dixon, F. J. Adv. Immun. 37, 269–390 (1985). 11. Wofsky, D., Hardy, R. R. & Seaman, W. E. J. Immun. 132, 2686–2689 (1984). 12. Hang, L., Theofilopoulos, A. N. & Dixon, F. J. /. exp. Med. 155, 1690–1701 (1982). 13. Kelley, V. & Roths, J. B. Clin. Immunopath. 37, 220–229 (1985). 14. Notman, D. D., Kurata, N. & Tan, E. N. Ann. intern. Med. 83, 464–469 (1975). 15. Munthe, E. & Natvig, J. B. Clin. exp. Immun. 12, 55–70 (1972). 16. Youinou, P. Y., Morrow, J. W., Lettin, A. W. F., Lydyard, P. M. & Roitt, I. M. Scand. J. Immun. 20, 307–315 (1984). 17. Theofilopoulos, A. N., Shawler, D. L., Eisenberg, R. A. & Dixon, F. J. / exp. Med. 151, 446–466 (1980). 18. Portanova, J. P., Claman, H. N. & Kotzin, B. L. J. Immun. 135, 3850–3856 (1985). 19. Shores, E. A., Eisenberg, R. A. & Cohen, P. L. /. Immun. 136, 3662–3667 (1986). 20. Rappard–Van Der Veen, F. M. J. Immun. 132, 1814–1819 (1984). 21. Nelson, J. L., Nardella, F. A., Opplinger, I. R. & Mannik, M. J. Immun. 138, 1391–1396 (1987). 22. Corbet, S., Milili, M., Fougereau, M. & Schiff, C. J. Immun. 138, 932–939 (1987). 23. Jukes, T. H. & Kling, J. L. Nature 281, 605–606 (1979). 24. Wu, T. T. & Kabat, E. A. /. exp. Med. 132, 211–250 (1970). 25. Kabat, E., Wu, T. T., Bilofsky, H., Reid–Miller, M. & Perry, H. Sequences of Proteins of Immunological Interest (US Govt Printing Office, Bethesda, Maryland, 1983). 26. Segal, D. et al. Proc. Natn. Acad. Sci. U.S.A. 71, 4298–4302 (1974). 27. Amit, A. G., Mariuzza, R. A. Phillips, S.E.V. & Poljak, R. J. Nature 313, 156–158 (1985). 28. McKean, D. K. et al. Proc. natn. Acad. Sci. U.S.A. 81, 3180–3186 (1984). 29. Claflin, J. L. & Williams, K. Curr. Top. Micro. Immun. 81, 107–109 (1978). 30. Andersson, J. & Melchers, F. Curr. Top. Micro. Immun. 81, 130–132 (1978). 31. Claflin, J. L., Berry, J., Flaherty, D. & Dunnick, W. / Immun. 138, 3060–3069 (1987). 32. Nemazee, D. J. exp. Med. 161, 242–256 (1985). 33. Coulie, P. & Van Snick, J. /. exp. Med. 161, 88–92 (1985). 34. Tarkowski, A., Czerinsky, C. & Nilsonn, L.–A. Clin. exp. Immun. 58, 7–12 (1984). 35. Cohen, P. L. et al. Cell. Immun. 96, 448–454 (1985). 36. Marshak–Rothstein, A. et al. J. Immun. 133, 2491–2497 (1978). 37. Van Snick, J. L., Stassin, V. & De Lestre, B. J. exp. Med. 157, 1006–1019. 38. Potter, M., Newell, J. B., Rudikoff, S. & Haber, E. Molec. Immun. 19, 1619–1630 (1982). 39. Brodeur, P. H. & Riblet, R. Eur. J. Immun. 14, 922–930, (1984). 40. Winter, E., Radbruch, A. & Krawinkel, U. EMBOJ. 4, 2861–2867 (1985). 41. Kurosawa, Y. & Tonegawa, S. J. exp. Med. 155, 201–218 (1982).
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Shlomchik, M., Marshak-Rothstein, A., Wolfowicz, C. et al. The role of clonal selection and somatic mutation in autoimmunity. Nature 328, 805–811 (1987). https://doi.org/10.1038/328805a0
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DOI: https://doi.org/10.1038/328805a0
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