INVOLVEMENT OF LFA-1 INTRACELLULAR ADHESION MOLECULE-DEPENDENT CELL-ADHESION IN CD40-MEDIATED INHIBITION OF HUMAN B-LYMPHOMA CELL-DEATH INDUCED BY SURFACE IGM CROSS-LINKING

B cells have been shown to receive negative signals for their growth t hrough crosslinking of surface IgM (sIgM), and it has been demonstrate d that anti-IgM Abs induce B cell death. Proliferation of B cells in r esponse to Ag stimulation in vivo may thus require additional signals that inhibit the sIgM-transduced negative signals. Signaling through C D40 has been proposed as a candidate for such costimulatory signals. T o investigate the role of CD40-transduced signals in sIgM-mediated B c ell death, we used a human B cell line (DND-39) that expresses sIgM, s IgD, and CD40. Crosslinking of sIgM, but not sIgD, by Abs induced DND- 39 cell death. The dying cells showed the morphology of apoptosis and DNA fragmentation. Anti-CD40 Abs induced homotypic adhesion of DND-39 cells and rescued them from anti-IgM Ab-induced cell death. Anti-CD40 Abs inhibited anti-IgM Ab-induced cell death when added within 3 h aft er stimulation with anti-IgM Ab. Treatment with Abs against CD11a, CD1 8, or CD54 inhibited not only the homotypic adhesion but also the inhi bition of anti-IgM Ab-induced apoptosis by anti-CD40 Ab. CD11a antisen se decreased the surface CD11a expression, the anti-CD40 Ab-induced ho motypic adhesion, and the inhibitory effect of anti-CD40 Ab on anti-Ig M Ab-induced apoptosis. The data show that LFA-1/ICAM-1-dependent cell adhesion induced by signaling through CD40 plays an important role in the inhibition of anti-IgM Ab-induced apoptosis of DND-39 cells.