Microfilament assembly is involved in B-cell apoptosis

Crosslinking of the B-cell antigen receptor (BCR) initiates a chain of reac tions which culminate in a number of biologic responses, including entry in to the cell cycle or cell death. The signals and processes which lead to ce ll death are slowly being unraveled. Based on the dramatic changes in cell shape which occur during progression of the apoptotic response, activation of cytoskeletal assembly may be critical as this appears to be essential to the mitogenic response. In this study, we demonstrate that crosslinking of the human BCR with anti-IgM antibodies results in the rapid assembly of ac tin. Our data also suggest that this conversion of G- to F-actin may be a p rerequisite for the apoptosis response, as prevention of this conversion by botulinum C-2 toxin or cytochalasin D results in rescue of the cells from apoptosis. Prevention of tyrosine kinase activation, disruption of microfil ament assembly, and rescue of B lymphocytes from apoptosis imply that tyros ine phosphorylation is needed for both microfilament assembly and apoptosis . In each instance where microfilament assembly is inhibited, anti-IgM-indu ced activation of the protease CPP32 (caspase) is also inhibited. Tak;en to gether, these results suggest that the microfilament system is actively inv olved in delivering signals for apoptosis. (C) 1999 Academic Press.