Abstract

B lymphocyte development is characterized by deletion via apoptosis of immature cells that are insufficiently stimulated. We have previously demonstrated that crosslinking of the B cell receptor (BCR) using anti-IgM antibodies (αIgM) (2 μg/ml) in Ramos B lymphoblastoid cells causes deletion of 30–40% of cells by apoptosis in 24 h. Addition of the potent lipid mediator platelet-activating factor (10−7M) to αIgM stimulated Ramos cells significantly decreases the number of apoptotic cells as measured by annexin V labeling. We have characterized the phenotype of Ramos cells that have not become apoptotic following BCR stimulation. In these cells, there is a significant decrease in the surface expression of the VLA-4 adhesion molecule (31% of control expression) and surface IgM expression (sIgM) (53% of control expression). Significantly fewer cells co-incubated with platelet-activating factor (PAF) underwent apoptosis, and the remaining cells maintained control levels of VLA-4 (104% of control expression) and sIgM expression (104% of control). All of these protective effects were inhibited by the specific PAF receptor antagonist, WEB 2170. The action of PAF on αIgM induced apoptosis was not inhibited by either cycloheximide or cytochalasin B, suggesting thatde novoprotein synthesis and F-actin polymerization were not implicated in the rescue of Ramos cells by PAF. In contrast, the ability of PAF to maintain sIgM and VLA-4 expression at control levels was inhibited by cycloheximide (7.5 μg/ml). Cytochalasin B (5 μg/ml) had no effect on sIgM expression but blocked the decrease in VLA-4 expression mediated by αIgM. These data indicate that PAF's effect on rescuing and maintaining αIgM stimulated Ramos B cells is mediated via at least two pathways. Abrogation of apoptosis does not requirede novoprotein synthesis, while maintenance of sIgM and VLA-4 expression requires protein synthesis.

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