Advertisement

Autoimmunity pp 273-284 | Cite as

The Anti-DNA Knock-In Model of Systemic Autoimmunity Induced by the Chronic Graft-vs-Host Reaction

Protocol
  • 972 Downloads
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 102)

Summary

The injection of spleen cells from bm12 mice into C57BL/6 recipients induces a chronic graft-vs-host reaction characterized by systemic autoimmunity, including anti-double-stranded DNA (anti-dsDNA) autoantibodies and immune complex-type proliferative glomerulonephritis. If the B6 recipient mice express an anti-DNA Vh site-directed transgene, the repertoire is skewed even more toward the anti-DNA response. Over a period of several weeks, high titers of serum anti-DNA antibodies appear and the mice develop renal damage. This permits the examination of the role of somatic immunoglobulin genetics and B-cell tolerance in a model of systemic lupus erythematosus.

Key Words

Anti-DNA autoimmunity B cells GVH SLE tolerance 

References

  1. 1.
    Morris, S. C., Cheek, R. L., Cohen, P. L., and Eisenberg, R. A. (1990) Autoantibodies in chronic graft vs host result from cognate T-B interactions. J. Exp. Med. 171, 503–517.PubMedCrossRefGoogle Scholar
  2. 2.
    Eisenberg, R. A. and Cohen, P. L. (1983) Class II major histocompatibility antigens and the etiology of systemic lupus erythematosus. Clin. Immunol. Immunopathol. 29, 1–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Feuerstein, N., Chen, F., Madaio, M., Maldonado, M., and Eisenberg, R. A. (1999) Induction of autoimmunity in a transgenic model of B cell receptor peripheral tolerance: changes in coreceptors and B cell receptor-induced tyrosine-phosphoproteins. J. Immunol. 163, 5287–5297.PubMedGoogle Scholar
  4. 4.
    Chen, C., Prak, E. L., and Weigert, M. (1997) Editing disease-associated autoantibodies. Immunity 6, 97–105.PubMedCrossRefGoogle Scholar
  5. 5.
    Prak, E. L., Trounstine, M., Huszar, D., and Weigert, M. (1994) Light chain editing in kappa-deficient animals: a potential mechanism of B cell tolerance. J. Exp. Med. 180, 1805–1815.PubMedCrossRefGoogle Scholar
  6. 6.
    Chen, F., Maldonado, M. A., Madaio, M., and Eisenberg, R. A. (1998) The role of host (endogenous) T cells in chronic graft-vs-host autoimmune disease. J. Immunol. 161, 5880–5885.PubMedGoogle Scholar
  7. 7.
    Sekiguchi, D. R., Jainandunsing, S. M., Fields, M. L., Maldonado, M. A., Madaio, M. P., Erickson, J., et al. (2002) Chronic graft-vs-host in Ig knockin transgenic mice abrogates B cell tolerance in anti-double-stranded DNA B cells. J. Immunol. 168, 4142–4153.PubMedGoogle Scholar
  8. 8.
    Sekiguchi, D. R., Eisenberg, R. A., and Weigert, M. (2003) Secondary heavy chain rearrangement: a mechanism for generating anti-double-stranded DNA B cells. J. Exp. Med. 197, 27–39.PubMedCrossRefGoogle Scholar
  9. 9.
    Tse, H. Y., Kanamori, S., Walsh, W. D., and Hansen, T. H. (1985) The murine bm12 gene conversion provides evidence that T cells recognize predominantly Ia conformation. Proc. Natl. Acad. Sci. USA 82, 7058–7062.PubMedCrossRefGoogle Scholar
  10. 10.
    Morris, S. C., Cheek, R. L., Cohen, P. L., and Eisenberg, R. A. (1990) Allotypespecific immunoregulation of autoantibody production by host B cells in chronic graft-vs-host disease. J. Immunol. 144, 916–922.PubMedGoogle Scholar
  11. 11.
    Morris, S. C., Cohen, P. L., and Eisenberg, R. A. (1990) Experimental induction of systemic lupus erythematosus by recognition of foreign Ia. Clin. Immunol. Immunopathol. 57, 263–273.PubMedCrossRefGoogle Scholar
  12. 12.
    van der Veen, F. M., Rolink, A. G., and Gleichmann, E. (1982) Autoimmune disease strongly resembling systemic lupus erythematosus (SLE) in F1 mice undergoing graft-vs-host reaction (GVHR). Adv. Exp. Med. Biol. 149, 669–677.PubMedGoogle Scholar
  13. 13.
    Gleichmann, E., Van Elven, E. H., and Van der Veen, J. P. (1982) A systemic lupus erythematosus (SLE)-like disease in mice induced by abnormal T-B cell cooperation. Preferential formation of autoantibodies characteristic of SLE. Eur. J. Immunol. 12, 152–159.PubMedCrossRefGoogle Scholar
  14. 14.
    van Rappard-Van der Veen, F. M., Kiesel, U., Poels, L., Schuler, W., Melief, C. J., Landegent, J., et al. (1984) Further evidence against random polyclonal antibody formation in mice with lupus-like graft-vs-host disease. J. Immunol. 132, 1814–1820.Google Scholar
  15. 15.
    van Rappard-van der Veen, F. M., Kong, Y. M., Rose, N. R., Kimura, M., and Gleichmann, E. (1984) Injection of mouse thyroglobulin and/or adult thymectomy do not break tolerance to thyroglobulin during the lupus like graft vs host disease in mice. Clin. Exp. Immunol. 55, 525–534.Google Scholar
  16. 16.
    Chen, C., Nagy, Z., Prak, E. L., and Weigert, M. (1995) Immunoglobulin heavy chain gene replacement: a mechanism of receptor editing. Immunity 3, 747–755.PubMedCrossRefGoogle Scholar
  17. 17.
    Erikson, J., Radic, M. Z., Camper, S. A., Hardy, R. R., Carmack, C., and Weigert, M. (1991) Expression of anti-DNA immunoglobulin transgenes in non-autoimmune mice. Nature 349, 331–334.PubMedCrossRefGoogle Scholar
  18. 18.
    Fowler, E. and Cheng, N. (1983) Comparison of radioimmunoassay and ELISA methods for detection of antibodies to chromatin components. J. Immunol. Methods 62, 297–303.PubMedCrossRefGoogle Scholar
  19. 19.
    Shlomchik, M. J., Madaio, M. P., Ni, D., Trounstein, M., and Huszar, D. (1994) The role of B cells in lpr/lpr-induced autoimmunity. J. Exp. Med. 180, 1295–1306.PubMedCrossRefGoogle Scholar
  20. 20.
    Bradley, D. S., Jennette, J. C., Cohen, P. L., and Eisenberg, R. A. (1994) Chronic graft vs host disease-associated autoimmune manifestations are independently regulated by different MHC class II loci. J. Immunol. 152, 1960–1969.PubMedGoogle Scholar
  21. 21.
    Fisher, C. L., Eisenberg, R. A., and Cohen, P. L. (1988) Quantitation and IgG subclass distribution of antichromatin autoantibodies in SLE mice. Clin. Immunol. Immunopathol. 46, 205–213.PubMedCrossRefGoogle Scholar
  22. 22.
    Reap, E. A., Piecyk, M. L., Oliver, A., Sobel, E. S., Waldschmidt, T., Cohen, P. L., et al. (1996) Phenotypic abnormalities of splenic and bone marrow B cells in lpr and gld mice. Clin. Immunol. Immunopathol. 78, 21–29.PubMedCrossRefGoogle Scholar
  23. 23.
    Chen, C., Radic, M. Z., Erikson, J., Camper, S. A., Litwin, S., Hardy, R. R., et al. (1994) Deletion and editing of B cells that express antibodies to DNA. J. Immunol. 152, 1970–1982.PubMedGoogle Scholar
  24. 24.
    Bensinger, S. J., Bandeira, A., Jordan, M. S., Caton, A. J., and Laufer, T. M. (2001) Major histocompatibility complex class II-positive cortical epithelium mediates the selection of CD4(+)25(+) immunoregulatory T cells. J. Exp. Med. 194, 427–438.PubMedCrossRefGoogle Scholar
  25. 25.
    Bruijn, J. A., van Leer, E. H., Baelde, H. J., Corver, W. E., Hogendoorn, P. C., and Fleuren, G. J. (1990) Characterization and in vivo transfer of nephritogenic autoantibodies directed against dipeptidyl peptidase IV and laminin in experimental lupus nephritis. Lab. Invest. 63, 350–359.PubMedGoogle Scholar
  26. 26.
    Bruijn, J. A., Hogendoorn, P. C., Corver, W. E., van den Broek, L. J., Hoedemaeker, P. J., and Fleuren, G. J. (1990) Pathogenesis of experimental lupus nephritis: a role for anti-basement membrane and anti-tubular brush border antibodies in murine chronic graft-vs-host disease. Clin. Exp. Immunol. 79, 115–122.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2004

Authors and Affiliations

  1. 1.Division of Rheumatology, Department of MedicineUniversity of PennsylvaniaPhiladelphia

Personalised recommendations