PENETRATION OF ANTI-DNA ANTIBODIES INTO IMMATURE LIVE CELLS

Several data suggest that immature lymphoid cells are more prone to pe netration and therefore are affected more by antibodies than their mat ure counterparts. In this study, we examined the penetration of monocl onal anti-DNA antibodies in several models of immature cells. Results confirm that most anti-DNA antibodies penetrate larger proportions of immature cells than normal adult cells. It was also proven that anti-D NA antibodies induce larger fractions of immature cells to undergo apo ptosis than mature cells; however, there is not a numerical associatio n between penetration and apoptosis. Additionally, the penetration and induction of apoptosis of several anti-DNA monoclonal antibodies into U937 and NIH-3T3 cells followed a rather heterogeneous pattern. When mature and immature cells were stimulated polyclonally, it was shown t hat polyreactive antibodies might act as an accessory signal to induce apoptosis in immature cells. This process could contribute to the edi tion of the immune repertoire. We propose that naturally occurring pol yreactive antinuclear antibodies, through penetration and deletion of self-reacting cells, could participate, either as a unique or secondar y signal, in the mechanism of self tolerance. If these polyreactive an tibodies undergo affinity maturation, it is possible they may develop into pathogenic antibodies. (C) 1998 Academic Press