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)

• Published in: Scandinavian journal of immunology Vol. 31; no. 5; p. 583
• Main Authors: Smeland, E B, Holte, H, Kiil Blomhoff, H, Asheim, H C, Stokke, T, Torjesen, P, Funderud, S
• Format: Journal Article
• Language: English
• Published: England 01.05.1990
• Subjects: Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antigens, Differentiation - immunology; B-Lymphocytes - immunology; Calcium - metabolism; Cell Cycle - drug effects; Cell Division - drug effects; Histocompatibility Antigens - immunology; Humans; Immunoglobulin mu-Chains - metabolism; Leukocyte Common Antigens; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphokines - immunology; Phosphatidylinositols - metabolism; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins c-myc; RNA - biosynthesis; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/j.1365-3083.1990.tb02809.x

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.