INHIBITION OF POLYPHOSPHOINOSITIDE BREAKDOWN AND C-MYC INDUCTION ACCOMPANYING INHIBITION OF HUMAN B-CELL ACTIVATION BY 2 MONOCLONAL-ANTIBODIES AGAINST THE LEUKOCYTE COMMON ANTIGEN (CD45)

In this report we show that the two monoclonal anti‐CD45 antibodies, EO‐1 and FN‐I26, potently inhibit G0 to G1 transition and S phase entry in human B cells stimulated with anti‐μ and low molecular weight B‐cell growth factor. Both antibodies were found to inhibit anti‐μ‐induced inositol phospholipid breakdown and c‐myc mRNA induction. In contrast, EO‐I and FN‐I26 only partially inhibited the early anti‐μ‐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 IF5, which confers an activation of B cells without any detectable increase in [Ca2+]1 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. Copyright © 1990, Wiley Blackwell. All rights reserved