Ligand recognition by murine anti-DNA autoantibodies: II. Genetic analysis and pathogenicity

Patrick Swanson, Raymond L. Yung, Neal B. Blatt, Melissa A. Eagan, Jennifer M. Norris, Bruce C. Richardson, Kent J. Johnson, Gary D. Glick

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Abstract

Although anti-DNA autoantibodies are an important hallmark of lupus, the relationships among anti-DNA structure, reactivity, and pathogenicity have not been fully elucidated. To further investigate these relationships, we compare the variable genes and primary structure of eight anti-DNA mAbs previously obtained from an MRL/MpJ-lpr/lpr mouse along with the ability of three representative mAbs to induce nephritis in nonautoimmune mice using established adoptive transfer protocols. One monospecific anti-single- stranded (ss) DNA (11F8) induces severe diffuse proliferative glomerulonephritis in nonautoimmune mice whereas another anti-ssDNA with apparently similar in vitro binding properties (9F11) and an anti-double- stranded DNA (4B2) are essentially benign. These results establish a murine model of anti-DNA-induced glomerular injury resembling the severe nephritis seen in lupus patients and provide direct evidence that anti-ssDNA can be more pathogenic than anti-double-stranded DNA. In vitro binding experiments using both protein-DNA complexes and naive kidney tissue indicate that glomerular localization of 11F8 may occur by recognition of a planted antigen in vive. Binding to this antigen is DNase sensitive which suggests that DNA or a DNA-containing molecule is being recognized.

Original languageEnglish
Pages (from-to)1748-1760
Number of pages13
JournalJournal of Clinical Investigation
Volume97
Issue number7
Publication statusPublished - Apr 1 1996
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Swanson, P., Yung, R. L., Blatt, N. B., Eagan, M. A., Norris, J. M., Richardson, B. C., ... Glick, G. D. (1996). Ligand recognition by murine anti-DNA autoantibodies: II. Genetic analysis and pathogenicity. Journal of Clinical Investigation, 97(7), 1748-1760.