Suppression of the immune response by α fetoprotein. I. The effect of mouse α fetoprotein on the primary and secondary antibody response

Abstract

Mouse amniotic fluid was shown to contain a noncytotoxic inhibitor of primary γM and secondary γM, γA, and γG subclass splenic plaque forming cells in vitro to Sheep red blood cells (SRBC). The suppressive effect was not abolished by exhaustive dialysis or by absorption of mouse amniotic fluid (MAF) with SRBC. Polyacrylamide gel analysis showed that dialyzed MAF was composed of three major protein components: transferrin, albumin, and alpha fetoprotein (AFP). The selective removal of each of these proteins from MAF by affinity chromatography suggested that AFP was the immunosuppressive substance in MAF. This conclusion was verified by the demonstration that pure AFP suppressed in vitro antibody synthesis in microgram quantities whereas equivalent amount 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 amount of AFP in MAF. γA and γG plaque forming cell (PFC) responses were suppressed by a significantly lower concentration of AFP than was the γM PFC response. The degree of suppression was dependent on the time at which AFP was added to the cultures; MAF added to antigen stimulated cultures up to 24 hr after initiation of cultures was immunosuppressive whereas simular additions of MAF at 48 hr after initiation or later did not suppress. The duration of exposure of spleen cells to MAF in cultures without antigen necessary to achieve suppresion of a subsequent primary immune response was determined to be approximately 7 hr. The results suggest that AFP may have an immunoregulatory function. This has potentially important implications in the maternal fetal relationship, the immune capabilities of the fetus and newborn and in certain malignant and nonmalignant diseases in which AFP is elevated.