Inhibition of polyphosphoinositide breakdown and c-myc induction accompanying inhibition of human B-cell activation by two monoclonal antibodies against the leucocyte common antigen (CD45).
In this report we show that the two monoclonal anti-CD45 antibodies, EO-1 and FN-126, potently inhibit G0 to G1 transition and S phase entry in human B cells stimulated with anti-mu and low molecular weight B-cell growth factor. Both antibodies were found to inhibit anti-mu-induced inositol phospholipid breakdown and c-myc mRNA induction. In contrast, EO-1 and FN-126 only partially inhibited the early anti-mu-induced increase in cytoplasmic Ca2+ levels, both in normal and in Ca2(+)-depleted medium. B-cell activation provoked by 12-O-tetradecanoylphorbol 13-acetate (TPA) was not inhibited by these antibodies, except when using high concentrations of EO-1. In addition, both antibodies were found to inhibit G1 entry induced by the anti-CD20 antibody 1F5, which confers an activation of B cells without any detectable increase in [Ca2+]i or in phospholipid metabolism. This indicates that alternative mechanisms in addition to the inhibition of polyphosphoinositide (PI) breakdown are involved in the inhibitory action of these antibodies.
Department of Pathology, Norwegian Radium Hospital, Oslo.
E B
EB
Smeland
H
H
Holte
H
H
Kiil Blomhoff
H C
HC
Asheim
T
T
Stokke
P
P
Torjesen
S
S
Funderud
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000943:Antigens, Differentiation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000378:metabolism; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008222:Lymphokines / Q000276:immunology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016271:Proto-Oncogene Proteins c-myc; D012313:RNA / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D006649:Histocompatibility Antigens; D007148:Immunoglobulin mu-Chains; D008222:Lymphokines; D010716:Phosphatidylinositols; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; C058162:low molecular weight-B cell growth factor; D012313:RNA; D017493:Leukocyte Common Antigens; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium