SPLENIC B-LYMPHOCYTE PROGRAMMED CELL-DEATH IS PREVENTED BY NITRIC-OXIDE RELEASE THROUGH MECHANISMS INVOLVING SUSTAINED BCL-2 LEVELS

Incubation of ex vivo cultured mature B cells in the presence of nitri c oxide or nitric oxide-donor substances delays programmed cell death as determined by the appearance of DNA laddering in agarose gel electr ophoresis or by flowcytometry analysis of DNA. Nitric oxide also rescu es B cells from antigen-induced apoptosis but fails to provide a co-st imulatory signal that converts the signal elicited by the antigen into a proliferative response, The protective effects of nitric oxide agai nst programmed cell death can be reproduced by treatment of the cells with permeant analogues of cyclic GMP. Regarding the mechanisms by whi ch nitric oxide prevents apoptosis in B cells, we have observed that n itric oxide release prevents the drop in the expression of the protoon cogene bcl-2, both at the mRNA and protein levels, suggesting the exis tence of an unknown pathway that links nitric oxide signaling with Bcl -2 expression.