Effects of a novel immunosuppressive agent, FK506, on human B cell activation.
We examined the effect of new immunosuppressive agent, FK506, on the human B cell function, in comparison with that of cyclosporin A (CyA) and tried to define the discrete activation step(s) which is selectively affected by FK506 and CyA. We used polyclonal B cell activators, Staphylococcus aureus Cowan I (SAC) and pokeweed mitogen (PWM). We found that (i) the initial B cell activation process by PWM, which is on the basis of T cell-dependent manner, is susceptible to the inhibitory effects of FK506 and CyA, while initial B cell activation on the basis of T cell-independent manner by SAC is resistant to these drugs; (ii) they also inhibit helper factor production by T cells; (iii) once they are activated, the B cells become resistant to inhibition by the drugs; and (iv) on an equimolar basis, FK506 exhibits 100-fold greater inhibitory activity than does CyA. Thus FK506 mainly interferes with interactions between T cells and other cells which are essential for B cell activation process, resulting in inhibition of B cell function.
Department of Internal Medicine, Shimane Medical University, Izumo, Japan.
N
N
Suzuki
T
T
Sakane
T
T
Tsunematsu
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects*; D003524:Cyclosporins / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008211:Lymphocyte Cooperation; D011043:Pokeweed Mitogens; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D011043:Pokeweed Mitogens; D016559:Tacrolimus