Effects of trifluoperazine, a calmodulin antagonist, on rabbit T- and B-cell responses to mitogens and antigens

Trifluoperazine (TFP), an inhibitor of the calcium-binding protein, calmodulin (CaM), was used to asess the role of calmodulin in the responses of rabbit lymphoid cells to stimulation with mitogen and antigen. After binding goat anti-rabbit Fab antibody, rabbit B cells lose their surface immunoglobulin (Ig) through endocytosis and then reexpress this protein during the next 24 hr. This reexpression as markedly inhibited by TFP. The brief and early addition of TFP markedly inhibited the increase ( super(3)H)thymidine (Tdr) uptake by rabbit T cells treated with concanavalin A and B cells exposed to anti-Fab. TFP greatly inhibited the induction by keyhole limpet hemocyanin (KLH) of the in vitro syntheses of anitbody, Ig, and protein. The earlier the TFP the greater was the inhibition of induction of these syntheses. However, once induced, synthesis and secretion of antibody were not inhibited by TFP. TFP was not cytotoxic for either resting or mitogen-or antigen-stimulated LNC. The calcium-CaM complex may mediate an interaction between the ligand-occupied surface receptor and the cytoskeleton.