Suppression of the immune response by alpha-fetoprotein 1. The effect of mouse alpha-fetoprotein on the primary and secondary antibody response.

Mouse amniotic fluid (AF) was shown to contain a noncytotoxic inhibitor of primary immunoglobulin (Ig) M and secondary IgM IgA and IgG subclass splenic plaque forming cells (PFC) in vitro to sheep red blood cells. The suppressive effect was not abolished by exhaustive dialysis or by absorption of mouse AF with sheep erythrocytes. Polyacrylamide gel analysis showed that dialyzed mouse AF was composed of 3 major protein components transferrin albumin and alpha fetoprotein (AFP). Selective removal of each of these proteins from AF by affinity chromatography suggested that AFP was the immunosuppressive substance in mouse AF. This conclusion was verified by the demonstration that pure AFP suppressed in vitro antibody synthesis in mcg quantities whereas equivalent amounts of normal mouse serum transferrin or albumin did not. Dose-response studies showed that the effect of AFP in the isolated form was equivalent to the suppressive effect of comparable amounts of AFP in mouse AF. IgA and IgG PFC responses were suppressed by a significantly lower concentration of AFP than was the IgM PFC response. The degree of suppression was dependent on the time at which AFP was added to the cultures; mouse AF added to antigen-stimulated cultures up to 24 hours after initiation of cultures was immunosuppressive whereas similar additions of mouse AF at 48 hours after initiation or later did not suppress. Duration of exposure of spleen cells to mouse AF in cultures without antigen necessary to achieve suppression of a subsequent primary immune response was determined to be 8 hours. AFP therefore may have an immunoregulatory function.