SELECTIVE ACCUMULATION OF ANTIHISTONE ANTIBODIES IN GLOMERULI OF LUPUS-PRONE LPR MICE

Immunoglobulins were eluted from glomeruli of 50 lupus-prone, lpr mice and their physicochemical properties and specificity were compared wi th those in sera pooled from the same mice. Although immunoglobulins i n glomeruli had higher isoelectric points than those in sera, there we re no appreciable differences in the relative contents of neutral and acidic immunoglobulins between them. The proportion of IgG(3) subclass was slightly higher in glomerular than serum immunoglobulins. Both an ti-single-stranded and anti-double-stranded DNA antibodies were twofol d higher in glomerular than serum immunoglobulins, while anti-Sm antib odies were not recovered in glomerular eluate despite their high activ ity in serum. Antibodies in glomerular eluate reacted most strongly wi th histones, especially with core histones, while those in sera bound preferentially with histone H1, Sm-B, -B', and -D antigens, Since hist ones are very basic, they would have a higher affinity for negatively charged glomerular constituents, leading to an in situ formation ofimm une complexes involving fixed histones and their binding with antibodi es for the induction of nephritides. Otherwise, such immune complexes themselves might retain positive charges sufficient for an affinity wi th the glomerular basement membrane. These results indicate that histo ne-anti-histone anti-body system may play a role in the perpetuation o f murine lupus nephritis. (C) 1996 Academic Press, Inc.