Positive and negative signals transduced through surface immunoglobulins in human B cells.

Cross-linking of surface IgM and surface IgD by anti-IgM antibodies and anti-IgD antibodies, respectively, showed different effects on the growth of normal human peripheral blood B cells and the human B lymphoma cell line, B104. Only cross-linking of surface IgM transduced signals that inhibited cell division of peripheral blood B cells and B104 cells at the G2/M interphase. In B104 cells, the inhibition of cell division was followed by rapid B104 cell death. The negative signals were inhibited by cyclosporin A and FK-506 at lower concentrations than those that inhibited proliferation of the B cells. Anti-IgM antibody-induced B104 cell death was dependent on Ca2+ influx and macromolecular synthesis. B104 cells treated with anti-IgM antibodies showed neither DNA fragmentation or morphology of apoptosis but showed DNA single-strand breaks and morphology of necrosis. Nicotinamide inhibited anti-IgM antibody-induced B104 cell death and the involvement of poly(adenosine diphosphate-ribosyl)ation was suggested in the process of the B104 cell death. With regard to the intracellular mechanisms responsible for the different signals, however, no qualitative difference was detected in putative signal transducers, including tyrosine phosphorylated protein, phosphatidyl inositol turnover, Ca2+ influx, activation of protein kinase C, and messenger ribonucleic acid expression of c-fos and Egr-1 when surface IgM and surface IgD were crosslinked. Further investigations of the mechanisms responsible for the different signals transduced through surface IgM and surface IgD will provide better understanding of immunodeficiencies and autoimmune diseases.