Pc. Swanson et al., LIGAND RECOGNITION BY MURINE ANTI-DNA AUTOANTIBODIES .2. GENETIC-ANALYSIS AND PATHOGENICITY, The Journal of clinical investigation, 97(7), 1996, pp. 1748-1760
Although anti-DNA autoantibodies are an important hallmark of lupus, t
he relationships among anti-DNA structure, reactivity, and pathogenici
ty have not been fully elucidated, To further investigate these relati
onships, 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 n
onautoimmune mice using established adoptive transfer protocols. One m
onospecific anti-single-stranded (ss) DNA (11F8) induces severe diffus
e proliferative glomerulonephritis in nonautoimmune mice whereas anoth
er anti-ssDNA with apparently similar in vitro binding properties (9F1
1) and an anti-double-stranded DNA (4B2) are essentially benign, These
results establish a murine model of anti-DNA-induced glomerular injur
y resembling the severe nephritis seen in lupus patients and provide d
irect evidence that anti-ssDNA can be more pathogenic than anti-double
-stranded DNA, In vitro binding experiments using both protein-DNA com
plexes and naive kidney tissue indicate that glomerular localization o
f 11F8 may occur by recognition of a planted antigen in vivo. Binding
to this antigen is DNase sensitive which suggests that DNA or a DNA-co
ntaining molecule is being recognized.