DECREASE IN CAMP LEVELS PROMOTED BY CD48-CD2 INTERACTION CORRELATES WITH INHIBITION OF APOPTOSIS IN B-CELLS

The authors recently reported that CD2 ligation rescues B cells from a ntigen-induced apoptosis by up-regulation of intracellular Bcl-2 level s. However, the characterization of the early signals involved in apop tosis rescue by CD2 ligation has not been well established. In this co ntext, CD2 does not promote either phosphatidylinositol turnover or Ca 2+ mobilization in B cells. In this paper the authors show that CD2 in teraction with its ligand CD48 also reduces the apoptosis induced by f orskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthi ne and, to a much lesser extent, the apoptosis induced by cholera toxi n in murine B splenocytes. Using a cAMP detection system sensitive to the picomolar range, the authors demonstrate thar CD2-CD48 interaction decreases the intracellular cAMP concentrations induced by forskolin but not by cholera toxin. In comparison with the CD2-CD48 interaction, CD40-CD40 ligand interaction completely inhibits the apoptosis induce d by cAMP increases without affecting the intracellular cAMP levels pr omoted by forskolin or cholera toxin. These results indicate that CD2 can also control the apoptosis at the very early steps after receptor signalling, such as the adenylate cyclase activity. Given that heterot rimeric G-proteins can mediate the adenylate cyclase activity the auth ors suggest that CD2 signalling could act through these small proteins , which would explain the inability of CD2 signalling to rescue from t he apoptosis induced by cholera toxin, a Gs-protein activator. Convers ely, CD40 seems to control apoptosis further downstream of the cAMP-PK A pathway where the survival and apoptotic signals are confluent, whic h might therefore render it a more efficient system to block apoptosis .