bcl‐2 Regulation in Normal Resting Lymphocytes and Lymphoblasts

Expression of the bcl‐2 protein and bcl‐2 mRNA at the individual cell level was semiquantitatively examined in normal quiescent peripheral blood lymphocytes and pokeweed mitogen‐ or concanavalin A and interleukin‐2‐induced lymphoblasts in vitro by microscopic fluorometry using immunofluorescence and fluorescein‐labeled in situ hybridization. Approximately 90% of normal quiescent T and B lymphocytes expressed bcl‐2 protein at a level which was compatible with that of bcl‐2 mRNA. On the contrary, most mitogen‐induced lymphoblasts showed a posttranscriptional suppression of bcl‐2 protein expression. However, bcl‐2 protein was not downregulated by the posttranscriptional suppression in all lymphocytes activated in vitro, but approximately 15% of the lymphoblasts still expressed bcl‐2 protein at a higher level than nontransformed quiescent small lymphocytes; thus bcl‐2 protein expression in lymphoblasts showed a distinct bimodal pattern. Furthermore, it was supposed that lymphoblasts with no detectable bcl‐2 protein might fall into apoptosis but the remainder, expressing high levels of bcl‐2 protein, could escape apoptosis. Thus, the bcl‐2 gene may play an important role as a regulator of apoptosis in the human immune system.