Involvement of LFA-1/intracellular adhesion molecule-1-dependent cell adhesion in CD40-mediated inhibition of human B lymphoma cell death induced by surface IgM crosslinking.

B cells have been shown to receive negative signals for their growth through crosslinking of surface IgM (sIgM), and it has been demonstrated that anti-IgM Abs induce B cell death. Proliferation of B cells in response to Ag stimulation in vivo may thus require additional signals that inhibit the sIgM-transduced negative signals. Signaling through CD40 has been proposed as a candidate for such costimulatory signals. To investigate the role of CD40-transduced signals in sIgM-mediated B cell death, we used a human B cell line (DND-39) that expresses sIgM, sIgD, 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 after stimulation with anti-IgM Ab. Treatment with Abs against CD11a, CD18, or CD54 inhibited not only the homotypic adhesion but also the inhibition of anti-IgM Ab-induced apoptosis by anti-CD40 Ab. CD11a antisense decreased the surface CD11a expression, the anti-CD40 Ab-induced homotypic adhesion, and the inhibitory effect of anti-CD40 Ab on anti-IgM 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.