Cyclosporin A and FK506 block the negative signaling mediated by surface IgM cross-linking in normal human mature B cells.
Cross-linking of surface IgM (sIgM) or sIgD by anti-IgM Ab or anti-IgD Ab, respectively, induced DNA synthesis in peripheral blood B cells (PBL-B). Cell division, determined by the increase in the number of M phase cells, was also induced when PBL-B were stimulated with anti-IgD Ab plus IL-4 or Staphylococcus aureus Cowan I (SAC), but far less by stimulation with anti-IgM Ab plus IL-4. Anti-IgM Ab did not suppress the DNA synthesis induced by SAC or anti-IgD Ab plus IL-4, but it did suppress the cell division induced by them. Thus, sIgM cross-linking generates both positive and negative signaling to B-cell proliferation. Cyclosporin A (CSA) and FK506 suppressed DNA synthesis and cell division at relatively high concentrations. On the other hand, CSA and FK506 at lower concentrations blocked the anti-IgM Ab-generated inhibition of cell division without affecting DNA synthesis. Low concentrations of CSA did not affect the cell division induced by anti-IgD Ab plus IL-4 but did increase the cell division induced by SAC or anti-IgM Ab plus IL-4, suggesting that stimulation with SAC, as well as with anti-IgM Ab plus IL-4, generates both positive and negative signals to cell division, whereas sIgD lacks the ability to transduce negative signaling.
Yamaoka
K
K
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Kim
K M
KM
Ishigami
T
T
Higaki
Y
Y
Hata
D
D
Katamura
K
K
Mayumi
M
M
Mikawa
H
H
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D003864:Depression, Chemical; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008677:Metaphase; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4; D016572:Cyclosporine; D016559:Tacrolimus