PENETRATING ANTI-DNA MONOCLONAL-ANTIBODIES INDUCE ACTIVATION OF HUMANPERIPHERAL-BLOOD MONONUCLEAR-CELLS

Different studies have shown that some autoantibodies are able to pene trate into living cells and that this phenomenon has functional conseq uences, including apoptosis. We have explored the effect of anti-DNA a ntibodies (Ab) on the in vitro activation of peripheral blood mononucl ear cells (PBMNC) and found that a human polyclonal anti-DNA, IgG, whi ch efficiently penetrated living cells, was able to induce the express ion of different cell activation antigens in vitro such as CD69, CD71 or CD98 by PBMNC from normal individuals. However, the cell activation phenotype induced by anti-DNA Ab was considered anomalous since the e xpression of some activation antigens was not up-regulated, and others showed aberrant behaviour (such as down-regulation of ICAM-1 expressi on). Similar results were obtained using different murine anti-DNA mon oclonal antibodies (mAb). In addition, mAB that showed an efficient ab ility to penetrate living cells tended to have a greater effect on PBM NC activation. Anti-DNA Ab were also able to induce a noticeable expre ssion of CD95/Fas. These data indicate that penetrating anti-DNA Ab ar e able to induce an anomalous activation state in vitro in a significa nt fraction of PBMNC. We believe this effect may occur In vivo and cou ld have an important function in the pathogenesis of the immune dysreg ulation seen in SLE. (C) 1998 Academic Press