Modulation of polyclonal activation by plasma fibronectin and fibronectin fragments.

Modulation of activation of polyclonal IgM, IgG and IgM anti-DNA antibodies by plasma fibronectin (Fn) was studied because in some autoimmune diseases there appears to be a correlation between the increased level of Fn in the affected tissues and increased polyclonal B-cell activation. Fn caused a dose-dependent polyclonal activation of IgM, IgG and IgM anti-DNA antibody-secreting cells in cultures of mouse splenocytes. Fn significantly inhibited the generation of polyclonal antibodies by Fn-binding stimulants and did not significantly change the generation of polyclonal antibodies by the stimulants that do not bind Fn. Plasmin or trypsin digestion of Fn abolished both the polyclonal activating properties of Fn and the inhibitory effects of Fn that were selective for the Fn-binding polyclonal activators. Digestion of Fn with trypsin also generated immunosuppressive Fn fragments that inhibited polyclonal activation by both Fn-binding and non-binding bacteria. Under our culture conditions Fn or Fn digests were not mitogenic and had no effect on the mitogenicity of Fn-binding and non-binding stimulants. These results indicate that Fn can act as a polyclonal activator and that it can also modulate lymphocyte activation induced by other activators.