HISTONE MEDIATES GLOMERULAR DEPOSITION OF SMALL-SIZE DNA ANTI-DNA COMPLEX

Histone can mediate the binding of free DNA to the glomerular capillar y wall. We tested whether histone could mediate the deposition of pref ormed DNA-anti-DNA immune complex (IC). IC were generated using monocl onal anti-DNA Ab and excess of small size I-125-DNA; after further dig estion with DNase the IC, containing 5 mu g DNA (now 20 to 60 bp), was injected into the left kidney of rats. When given alone, only about 0 .2% of the IC bound in glomeruli. Prior injection of 200 mu g of core histones (H2A,H2B,H3,H4) resulted in high glomerular binding of the IC ; 18.1% of the injected dose (measured as I-125-DNA) was bound at 15 m inutes. Mouse immunoglobulin, representing the IC, could be seen in a capillary pattern. C3 was also present in a similar pattern, showing t hat complement had been activated. Discrete electron-dense deposits we re seen in a subendothelial and subepithelial localization at 15 minut es. Although about 1 mu g of DNA was deposited in the glomeruli, it co uld not be detected by indirect immunofluorescence or intercalating dy es. These studies provide direct evidence that histones can mediate th e binding of particular circulating DNA-anti-DNA immune complexes to t he glomerular capillary wall in vivo. If small size DNA fragments (<10 0 bp) are involved in lupus nephritis, our results provide a possible explanation for the frequent failure to detect DNA deposits in renal b iopsies from SLE patients.