Antibodies specific for gp40 inhibit cell-cell adhesion by cross-linking the protein on the surface of Dictyostelium purpureum

We have previously suggested a role for gp40 in cell‐cell adhesion in Dictyostelium purpureum from the fact that antibodies specific for this protein inhibited adhesion in an in vitro assay [Springer: Dev Biol 133:447–455, 1989]. To further confirm this role mutants lacking the protein were isolated and characterized. To our surprise, the mutants had normal adhesive properties both in vitro and in situ. These results lead us to the conclusion that gp40 is not necessary for the cell‐cell adhesions observed and may not be a molecule which directly participates in these adhesions. When studied further, we found that adhesion‐inhibitory antibodies were only effective as divalent IgG. Monovalent Fab fragments of the same antibodies could not inhibit adhesion. The inhibitory antibodies also caused the cells to remain rounded and incapable of attaching to plastic surfaces. We conclude that when divalent antibodies specific for gp40 cross‐link this protein on the cell surface a cytoskeletal change prevents them from attaching to substratum as well as to other cells, thereby inhibiting cell‐cell adhesion. We suggest that an alternative mechanism for inhibition of cell‐cell adhesion by divalent antibodies exists and should be considered before proposing a direct role for a protein in adhesion.