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. 1995 Mar;95(3):1398–1402. doi: 10.1172/JCI117793

Induction of cross-reactive anti-dsDNA antibodies in preautoimmune NZB/NZW mice by immunization with bacterial DNA.

G S Gilkeson 1, A M Pippen 1, D S Pisetsky 1
PMCID: PMC441482  PMID: 7883986

Abstract

To investigate the role of antigen drive in anti-double-stranded (ds) DNA production, the antibody response induced in lupus-prone NZB/NZW mice by E. coli (EC) dsDNA was evaluated. Preautoimmune NZB/NZW female mice were immunized with complexes of EC dsDNA with methylated bovine serum albumin (mBSA) in complete Freund's adjuvant; control mice received either mBSA complexes with calf thymus (CT) dsDNA or mBSA alone in adjuvant. IgG antibody responses were assessed by ELISA. Similar to normal mice, immunized NZB/NZW mice produced significant levels of anti-dsDNA when measured with EC dsDNA as antigen. Whereas normal mice produce antibodies which are specific for the immunizing bacterial DNA, NZB/NZW mice produced antibodies that bound crossreactively to CT dsDNA by ELISA. Furthermore, the induced antibodies resembled lupus anti-DNA in their fine specificity for polynucleotide antigens and reactivity with Crithidia luciliae DNA. Despite their response to EC dsDNA, NZB/NZW mice immunized with CT dsDNA failed to generate significant anti-dsDNA responses. These results provide further evidence for the enhanced immunogenicity of bacterial DNA and suggest that immune cell abnormalities in NZB/NZW mice promote the generation of crossreactive autoantibody responses when confronted with a foreign DNA.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Apperloo-Renkema H. Z., Bootsma H., Mulder B. I., Kallenberg C. G., van der Waaij D. Host-microflora interaction in systemic lupus erythematosus (SLE): colonization resistance of the indigenous bacteria of the intestinal tract. Epidemiol Infect. 1994 Apr;112(2):367–373. doi: 10.1017/s0950268800057770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Babcock S. K., Appel V. B., Schiff M., Palmer E., Kotzin B. L. Genetic analysis of the imperfect association of H-2 haplotype with lupus-like autoimmune disease. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7552–7555. doi: 10.1073/pnas.86.19.7552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. CASALS S. P., FRIOU G. J., MYERS L. L. SIGNIFICANCE OF ANTIBODY TO DNA IN SYSTEMIC LUPUS ERYTHEMATOSUS. Arthritis Rheum. 1964 Aug;7:379–390. doi: 10.1002/art.1780070404. [DOI] [PubMed] [Google Scholar]
  4. Desai D. D., Krishnan M. R., Swindle J. T., Marion T. N. Antigen-specific induction of antibodies against native mammalian DNA in nonautoimmune mice. J Immunol. 1993 Aug 1;151(3):1614–1626. [PubMed] [Google Scholar]
  5. Fredriksen K., Brannsether B., Traavik T., Rekvig O. P. Antibodies to viral and mammalian native DNA in response to BK virus inoculation and subsequent immunization with calf thymus DNA. Scand J Immunol. 1991 Jul;34(1):109–119. doi: 10.1111/j.1365-3083.1991.tb01526.x. [DOI] [PubMed] [Google Scholar]
  6. Gilkeson G. S., Bloom D. D., Pisetsky D. S., Clarke S. H. Molecular characterization of anti-DNA antibodies induced in normal mice by immunization with bacterial DNA. Differences from spontaneous anti-DNA in the content and location of VH CDR3 arginines. J Immunol. 1993 Aug 1;151(3):1353–1364. [PubMed] [Google Scholar]
  7. Gilkeson G. S., Grudier J. P., Karounos D. G., Pisetsky D. S. Induction of anti-double stranded DNA antibodies in normal mice by immunization with bacterial DNA. J Immunol. 1989 Mar 1;142(5):1482–1486. [PubMed] [Google Scholar]
  8. Gilkeson G. S., Pritchard A. J., Pisetsky D. S. Specificity of anti-DNA antibodies induced in normal mice by immunization with bacterial DNA. Clin Immunol Immunopathol. 1991 May;59(2):288–300. doi: 10.1016/0090-1229(91)90025-6. [DOI] [PubMed] [Google Scholar]
  9. Hirose S., Wakiya M., Kawano-Nishi Y., Yi J., Sanokawa R., Taki S., Shimamura T., Kishimoto T., Tsurui H., Nishimura H. Somatic diversification and affinity maturation of IgM and IgG anti-DNA antibodies in murine lupus. Eur J Immunol. 1993 Nov;23(11):2813–2820. doi: 10.1002/eji.1830231114. [DOI] [PubMed] [Google Scholar]
  10. Krishnan M. R., Marion T. N. Structural similarity of antibody variable regions from immune and autoimmune anti-DNA antibodies. J Immunol. 1993 Jun 1;150(11):4948–4957. [PubMed] [Google Scholar]
  11. Lake R. A., Morgan A., Henderson B., Staines N. A. A key role for fibronectin in the sequential binding of native dsDNA and monoclonal anti-DNA antibodies to components of the extracellular matrix: its possible significance in glomerulonephritis. Immunology. 1985 Feb;54(2):389–395. [PMC free article] [PubMed] [Google Scholar]
  12. Mackworth-Young C., Schwartz R. S. Autoantibodies to DNA. Crit Rev Immunol. 1988;8(3):147–173. [PubMed] [Google Scholar]
  13. Madaio M. P., Hodder S., Schwartz R. S., Stollar B. D. Responsiveness of autoimmune and normal mice to nucleic acid antigens. J Immunol. 1984 Feb;132(2):872–876. [PubMed] [Google Scholar]
  14. Messina J. P., Gilkeson G. S., Pisetsky D. S. The influence of DNA structure on the in vitro stimulation of murine lymphocytes by natural and synthetic polynucleotide antigens. Cell Immunol. 1993 Mar;147(1):148–157. doi: 10.1006/cimm.1993.1055. [DOI] [PubMed] [Google Scholar]
  15. O'Keefe T. L., Datta S. K., Imanishi-Kari T. Cationic residues in pathogenic anti-DNA autoantibodies arise by mutations of a germ-line gene that belongs to a large VH gene subfamily. Eur J Immunol. 1992 Mar;22(3):619–624. doi: 10.1002/eji.1830220302. [DOI] [PubMed] [Google Scholar]
  16. Pisetsky D. S. Anti-DNA antibodies in systemic lupus erythematosus. Rheum Dis Clin North Am. 1992 May;18(2):437–454. [PubMed] [Google Scholar]
  17. Pisetsky D. S., Grudier J. P., Gilkeson G. S. A role for immunogenic DNA in the pathogenesis of systemic lupus erythematosus. Arthritis Rheum. 1990 Feb;33(2):153–159. doi: 10.1002/art.1780330202. [DOI] [PubMed] [Google Scholar]
  18. Radic M. Z., Mascelli M. A., Erikson J., Shan H., Shlomchik M., Weigert M. Structural patterns in anti-DNA antibodies from MRL/lpr mice. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 2):933–946. doi: 10.1101/sqb.1989.054.01.108. [DOI] [PubMed] [Google Scholar]
  19. Sabbaga J., Line S. R., Potocnjak P., Madaio M. P. A murine nephritogenic monoclonal anti-DNA autoantibody binds directly to mouse laminin, the major non-collagenous protein component of the glomerular basement membrane. Eur J Immunol. 1989 Jan;19(1):137–143. doi: 10.1002/eji.1830190122. [DOI] [PubMed] [Google Scholar]
  20. Shlomchik M. J., Aucoin A. H., Pisetsky D. S., Weigert M. G. Structure and function of anti-DNA autoantibodies derived from a single autoimmune mouse. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9150–9154. doi: 10.1073/pnas.84.24.9150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shlomchik M., Mascelli M., Shan H., Radic M. Z., Pisetsky D., Marshak-Rothstein A., Weigert M. Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med. 1990 Jan 1;171(1):265–292. doi: 10.1084/jem.171.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Terada K., Okuhara E., Kawarada Y. Antigen DNA isolated from immune complexes in plasma of patients with systemic lupus erythematosus hybridizes with the Escherichia coli lac Z gene. Clin Exp Immunol. 1991 Jul;85(1):66–69. doi: 10.1111/j.1365-2249.1991.tb05683.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Theofilopoulos A. N., Dixon F. J. Etiopathogenesis of murine SLE. Immunol Rev. 1981;55:179–216. doi: 10.1111/j.1600-065x.1981.tb00343.x. [DOI] [PubMed] [Google Scholar]
  24. Theofilopoulos A. N., Kofler R., Singer P. A., Dixon F. J. Molecular genetics of murine lupus models. Adv Immunol. 1989;46:61–109. doi: 10.1016/s0065-2776(08)60651-3. [DOI] [PubMed] [Google Scholar]

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