The distinct effects of FK506 on the activation, proliferation, and differentiation of human B lymphocytes.
We examined the effect of FK506 on the activation, proliferation and differentiation of human B lymphocytes in vitro. FK506 inhibited the proliferative response of resting B cells induced by Staphylococcus aureus Cowan strain I (SAC) and phorbol myristate acetate (PMA) in a dose-dependent manner. Inhibition of cell proliferation by FK506 was caused by a selective block of G0 to G1 phase transition leading to cell arrest. In addition, the proliferative response of in vivo-activated B cells and lymphokine-driven B cell proliferation were also found to be sensitive to FK506. Interestingly, FK506 did not affect the expression of activation antigens such as CD23, IL-2 receptor (CD25), and transferrin receptor (CD71). Finally, FK506 had little effect on B cell antibody generation in a T cell-independent system. Conversely, FK506 suppressed neither proliferation nor immunoglobulin secretion in a human B lymphoblastoid cell line. These results indicate that FK506 has discrete effects on the different stages of the B cell maturation.
D000921:Antibody-Producing Cells / Q000187:drug effects; D001402:B-Lymphocytes / Q000737:chemistry / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007700:Kinetics; D007958:Leukocyte Count / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D012313:RNA / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000502:physiology; D016559:Tacrolimus / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D007136:Immunoglobulins; D012313:RNA; D004247:DNA; D013755:Tetradecanoylphorbol Acetate; D016559:Tacrolimus