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.
Smeland
E B
EB
Department of Pathology, Norwegian Radium Hospital, Oslo.
Holte
H
H
Kiil Blomhoff
H
H
Asheim
H C
HC
Stokke
T
T
Torjesen
P
P
Funderud
S
S
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