THE EXPRESSION OF ACIDIC RIBOSOMAL PHOSPHOPROTEINS ON THE SURFACE-MEMBRANE OF DIFFERENT TISSUES IN AUTOIMMUNE AND NORMAL MICE WHICH ARE THETARGET MOLECULES FOR ANTI-DOUBLE-STRANDED DNA ANTIBODIES

Affinity-purified polyclonal anti-double-stranded DNA (anti-dsDNA) ant ibodies from patients with systemic lupus erythematosus (SLE) exert a cytostatic effect on cultured rat glomerular mesangial cells (MC). The cognate antigens expressed on the surface of MC have been proved to b e acidic ribosomal phosphoproteins (P proteins) in our previous study. The mesangial cytostatic effect of anti-dsDNA antibodies is attribute d to the cross-reactivity of the antibodies with membrane-expressed P proteins, but not to the effect of minute amounts of anti-ribosomal P proteins antibodies contained in the anti-dsDNA preparations. Immunofl uorescence staining of the native cells demonstrated that anti-dsDNA a ntibodies bound to the surface of rat mesangial cells, rat brain astro cytes (RBA-1) and mouse fibroblasts (3T3). Anti-dsDNA antibodies also exert potent cytostatic effects on these cells in a dose-dependent man ner. In addition, the plasma membranes of different cell lines and tis sues from normal and autoimmune mice were isolated and probed by anti- dsDNA antibodies in Western blot analysis. We found the actively proli ferating cells such as MC, RBA-1 and 3T3 may express both P0 (38 000 M W) and P1 (19 000 MW) on the surface membrane. In addition, the kidney , liver and spleen from either autoimmune MRL-lpr/lpr or BALB/c mice m ay constantly express PO protein, but the expression of P1 is inconsis tent. In contrast, brain and muscle from either mice failed to express P proteins on their surface. Unexpectedly, a high molecular weight su bstance (larger than 205 000 MW) with unknown nature appears in the me mbrane of brain and muscle tissues in both mice. Immunoprecipitation o f the surface-biotinylated MC-lysate by anti-dsDNA antibodies further confirmed that P1 (19 000 MW) and P2 (17 000 MW) are really expressed on the cell surface. These results suggest that P proteins expressed o n the surface of different tissues become the targets for anti-dsDNA a ntibodies mediating pleomorphic tissue damage in patients with SLE.