Molecular Basis of B‐Cell Activation

The present experiments were performed in an attempt to investigate the nature of the surface receptor on B lymphocytes responsible for triggering of these cells. B‐cell mitogenicity of unsubstituted dextrans, quantitated by activation of DNA and antibody synthesis was detected only if the ligand had a MVC higher than 7 × 104. Above this threshold mitogenicity increased linearly with the log of the MW Substitution of the polymeric structure with lipid residues did not result in increased mitogenicity of the conjugate. However, sulphate substitution of the sugar units greatly enhanced the ability of the conjugates to activate DNA synthesis and. to a much smaller extent, antibody synthesis. Mitogenicity of sulphate derivatives was independent of their MW. Another polyanionic derivative (carboxymethyl) did not show increased mitogenicity. whereas a low‐MW compound very similar to dextran sulphate (pentosan sulphate) was highly active. The activation induced by dextrans was immunologically nonspecific and caused induction of polyclonal antibody synthesis. The activated cells presumably belong to a subset of B cells at a rather premature stage of differentiation. These findings suggest that the mitogenic signal is delivered to the cells by single sites at the membrane. These sites appear to have the capacity to interact with polysaccharide structures or releated conformations The polymeric structure of the active ligands is not a necessary requirement for mitogenicity and seems to have the accessory function of providing multipoint binding to low‐affinity receptors.