Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1985 Apr;60(1):159–168.

In vivo clearance and tissue uptake of an anti-DNA monoclonal antibody and its complexes with DNA.

E Ben Chetrit, E H Dunsky, S Wollner, D Eilat
PMCID: PMC1576988  PMID: 3874013

Abstract

In vivo clearance and tissue localization of a purified mouse anti-DNA monoclonal antibody (MoAb) (A52 IgG2b) and its complexes with DNA were studied in normal BALB/c and autoimmune NZB/NZW mice. The plasma half-life of the autoantibody in both mouse strains was significantly shorter (T 1/2 = 10-15 min), compared with that of purified NZB myeloma proteins (T 1/2 greater than or equal to 180 min). DNA antigen and DNA-A52 IgG complexes in antibody excess were cleared very rapidly (T 1/2 = 4-8 min), while complexes formed in antigen excess persisted in the circulation much longer (T 1/2 = 60 min). Organ studies showed that the anti-DNA MoAb was transiently retained by the liver and the spleen but demonstrated a particular affinity for the kidney tissue. We suggest that tissue damage in SLE glomerulonephritis may be facilitated by direct interaction of anti-DNA antibodies with glomerular components.

Full text

PDF
159

Selected References

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

  1. Agnello V., Koffler D., Eisenberg J. W., Winchester R. J., Kundel H. G. C1g precipitins in the sera of patients with systemic lupus erythematosus and other hypocomplementemic states: characterization of high and low molecular weight types. J Exp Med. 1971 Sep 1;134(3 Pt 2):228s–241s. [PubMed] [Google Scholar]
  2. Ballard D. W., Voss E. W., Jr Monoclonal murine anti-nucleic acid antibody with double-stranded specificity. Mol Immunol. 1982 Jun;19(6):793–799. doi: 10.1016/0161-5890(82)90005-0. [DOI] [PubMed] [Google Scholar]
  3. Batsford S. R., Takamiya M., Vogt A. A model of in situ immune complex glomerulonephritis in the rat employing cationized ferritin. Clin Nephrol. 1980 Nov;14(5):211–216. [PubMed] [Google Scholar]
  4. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bolton A. E., Hunter W. M. The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J. 1973 Jul;133(3):529–539. doi: 10.1042/bj1330529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Border W. A., Ward H. J., Kamil E. S., Cohen A. H. Induction of membranous nephropathy in rabbits by administration of an exogenous cationic antigen. J Clin Invest. 1982 Feb;69(2):451–461. doi: 10.1172/JCI110469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bruneau C., Benveniste J. Circulating DNA:anti-DNA complexes in systemic lupus erythematosus. Detection and characterization by ultracentrifugation. J Clin Invest. 1979 Jul;64(1):191–198. doi: 10.1172/JCI109439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Caulfield J. P., Farquhar M. G. Distribution of annionic sites in glomerular basement membranes: their possible role in filtration and attachment. Proc Natl Acad Sci U S A. 1976 May;73(5):1646–1650. doi: 10.1073/pnas.73.5.1646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chused T. M., Steinberg A. D., Talal N. The clearance and localization of nucleic acids by New Zealand and normal mice. Clin Exp Immunol. 1972 Dec;12(4):465–476. [PMC free article] [PubMed] [Google Scholar]
  11. Dang H., Harbeck R. J. The in vivo and in vitro glomerular deposition of isolated anti-double-stranded-DNA antibodies in NZB/W mice. Clin Immunol Immunopathol. 1984 Feb;30(2):265–278. doi: 10.1016/0090-1229(84)90061-8. [DOI] [PubMed] [Google Scholar]
  12. Eilat D., Hochberg M., Fischel R., Laskov R. Antibodies to RNA from autoimmune NZB/NZW mice recognize a similar antigenic determinant and show a large idiotypic diversity. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3818–3822. doi: 10.1073/pnas.79.12.3818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Eilat D., Hochberg M., Pumphrey J., Rudikoff S. Monoclonal antibodies to DNA and RNA from NZB/NZW F1 mice: antigenic specificities and NH2 terminal amino acid sequences. J Immunol. 1984 Jul;133(1):489–494. [PubMed] [Google Scholar]
  14. Emlen W., Mannik M. Clearance of circulating DNA-anti-DNA immune complexes in mice. J Exp Med. 1982 Apr 1;155(4):1210–1215. doi: 10.1084/jem.155.4.1210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Emlen W., Mannik M. Effect of DNA size and strandedness on the in vivo clearance and organ localization of DNA. Clin Exp Immunol. 1984 Apr;56(1):185–192. [PMC free article] [PubMed] [Google Scholar]
  16. Faaber P., Capel P. J., Rijke G. P., Vierwinden G., van de Putte L. B., Koene R. A. Cross-reactivity of anti-DNA antibodies with proteoglycans. Clin Exp Immunol. 1984 Mar;55(3):502–508. [PMC free article] [PubMed] [Google Scholar]
  17. Finbloom D. S., Plotz P. H. Studies of reticuloendothelial function in the mouse with model immune complexes. II. Serum clearance, tissue uptake, and reticuloendothelial saturation in NZB/W mice. J Immunol. 1979 Oct;123(4):1600–1603. [PMC free article] [PubMed] [Google Scholar]
  18. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  19. Frank M. M., Lawley T. J., Hamburger M. I., Brown E. J. NIH Conference: Immunoglobulin G Fc receptor-mediated clearance in autoimmune diseases. Ann Intern Med. 1983 Feb;98(2):206–218. doi: 10.7326/0003-4819-98-2-218. [DOI] [PubMed] [Google Scholar]
  20. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  21. Hahn B. H. Characteristics of pathogenic subpopulations of antibodies to DNA. Arthritis Rheum. 1982 Jul;25(7):747–752. doi: 10.1002/art.1780250706. [DOI] [PubMed] [Google Scholar]
  22. Hahn B. H., Ebling F., Freeman S., Clevinger B., Davie J. Production of monoclonal murine antibodies to DNA by somatic cell hybrids. Arthritis Rheum. 1980 Aug;23(8):942–945. doi: 10.1002/art.1780230811. [DOI] [PubMed] [Google Scholar]
  23. Izui S., Lambert P. H., Miescher P. A. Failure to detect circulating DNA--anti-DNA complexes by four radioimmunological methods in patients with systemic lupus erythematosus. Clin Exp Immunol. 1977 Dec;30(3):384–392. [PMC free article] [PubMed] [Google Scholar]
  24. Izui S., Lambert P. H., Miescher P. A. In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA. A possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus. J Exp Med. 1976 Aug 1;144(2):428–443. doi: 10.1084/jem.144.2.428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kanwar Y. S., Farquhar M. G. Isolation of glycosaminoglycans (heparan sulfate) from glomerular basement membranes. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4493–4497. doi: 10.1073/pnas.76.9.4493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Klotz J. L., Phillips M. L., Miller M. M., Teplitz R. L. Monoclonal autoantibody production by hybrid cell lines. Clin Immunol Immunopathol. 1981 Mar;18(3):368–374. doi: 10.1016/0090-1229(81)90130-6. [DOI] [PubMed] [Google Scholar]
  27. Koffler D., Carr R., Agnello V., Thoburn R., Kunkel H. G. Antibodies to polynucleotides in human sera: antigenic specificity and relation to disease. J Exp Med. 1971 Jul 1;134(1):294–312. doi: 10.1084/jem.134.1.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Koffler D., Schur P. H., Kunkel H. G. Immunological studies concerning the nephritis of systemic lupus erythematosus. J Exp Med. 1967 Oct 1;126(4):607–624. doi: 10.1084/jem.126.4.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Koike T., Nagasawa R., Nagata N., Shirai T. Specificity of mouse hybridoma antibodies to DNA. Immunol Lett. 1982 Feb;4(2):93–97. doi: 10.1016/0165-2478(82)90006-2. [DOI] [PubMed] [Google Scholar]
  30. Köhler G., Milstein C. Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. Eur J Immunol. 1976 Jul;6(7):511–519. doi: 10.1002/eji.1830060713. [DOI] [PubMed] [Google Scholar]
  31. Lambert P. H., Dixon F. J. Pathogenesis of the glomerulonephritis of NZB/W mice. J Exp Med. 1968 Mar 1;127(3):507–522. doi: 10.1084/jem.127.3.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Laskov R., Muller S., Hochberg M., Giloh H., Van Regenmortel M. H., Eilat D. Monoclonal autoantibodies to histones from autoimmune NZB/NZW F1 mice. Eur J Immunol. 1984 Jan;14(1):74–81. doi: 10.1002/eji.1830140114. [DOI] [PubMed] [Google Scholar]
  33. Lee J. S., Lewis J. R., Morgan A. R., Mosmann T. R., Singh B. Monoclonal antibodies showing sequence specificity in their interaction with single-stranded DNAs. Nucleic Acids Res. 1981 Apr 10;9(7):1707–1721. doi: 10.1093/nar/9.7.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Marion T. N., Lawton A. R., 3rd, Kearney J. F., Briles D. E. Anti-DNA autoantibodies in (NZB X NZW)F1 mice are clonally heterogeneous, but the majority share a common idiotype. J Immunol. 1982 Feb;128(2):668–674. [PubMed] [Google Scholar]
  35. Pisetsky D. S., Caster S. A. Binding specificity of a monoclonal anti-DNA antibody. Mol Immunol. 1982 May;19(5):645–650. doi: 10.1016/0161-5890(82)90364-9. [DOI] [PubMed] [Google Scholar]
  36. Pisetsky D. S., Peters D. V. A simple enzyme-linked immunosorbent assay for antibodies to native DNA. J Immunol Methods. 1981;41(2):187–200. doi: 10.1016/0022-1759(81)90242-8. [DOI] [PubMed] [Google Scholar]
  37. Rennke H. G., Cotran R. S., Venkatachalam M. A. Role of molecular charge in glomerular permeability. Tracer studies with cationized ferritins. J Cell Biol. 1975 Dec;67(3):638–646. doi: 10.1083/jcb.67.3.638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  39. Shoenfeld Y., Hsu-Lin S. C., Gabriels J. E., Silberstein L. E., Furie B. C., Furie B., Stollar B. D., Schwartz R. S. Production of autoantibodies by human-human hybridomas. J Clin Invest. 1982 Jul;70(1):205–208. doi: 10.1172/JCI110595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Steinman C. R. Circulating DNA in systemic lupus erythematosus. Isolation and characterization. J Clin Invest. 1984 Mar;73(3):832–841. doi: 10.1172/JCI111278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tron F., Charron D., Bach J. F., Talal N. Establishment and characterization of a murine hybridoma secreting monoclonal anti-DNA autoantibody. J Immunol. 1980 Dec;125(6):2805–2809. [PubMed] [Google Scholar]
  42. Winfield J. B., Faiferman I., Koffler D. Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis. J Clin Invest. 1977 Jan;59(1):90–96. doi: 10.1172/JCI108626. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES