INDUCTION OF ANTIHEPATITIS-B SURFACE-ANTIGEN (HBSAG) ANTIBODIES IN HBSAG PRODUCING TRANSGENIC MICE - A POSSIBLE WAY OF CIRCUMVENTING NONRESPONSE TO HBSAG

As a model for studying possible mechanisms of nonresponse toward hepatitis B surface antigen (HBsAg) in hepatitis B virus (HBV) carriers, we used transgenic (Tg) mice which constitutively express this antigen in the liver from before birth. The mice secrete large amounts of HBsAg particles into the sera without producing antibodies. Tg and control mice were immunized with either recombinant HBsAg particles of a different subtype, or with recombinant hybrid HBsAg particles carrying a human immunodeficiency virus (HIV) envelope determinant. The presence of determinants to which the mice are tolerant on the injected particles does not hamper the response to the foreign epitope. Moreover, a weak but significant anti-HBs response is clearly detectable in Tg mice immunized with these particles. Antibodies to epitopes carried by the transgenic antigen are made even after injection of homologous antigen, and a concomitant decrease in circulating HBsAg is observed. This immune response does not induce any liver damage. It was demonstrated that in these Tg mice, B cell self-tolerance toward HBsAg can be overcome by immunization. This phenomenon raises the possibility of designing more effective methods of immunotherapy for HBV carriers.