FcRn overexpression in transgenic animals results in robust immune response (P1069)

Abstract Our previous studies have shown that overexpression of the neonatal Fc receptor (FcRn) in transgenic animals (mice and rabbits) leads to (1) improved IgG protection; (2) larger numbers of antigen specific B cells; (3) generation of antibodies against weakly immunogenic antigens; (4) generation of antibodies against highly conserved antigens (breaking immune tolerance); (5) increased humoral diversity and (6) higher levels of circulating antibodies. FcRn transgenesis thus confers a number of practical benefits, including faster antibody production, higher antibody yields and improved generation of hybridomas for monoclonal antibody production. To gain additional insights into the mechanisms underlying this increase in humoral immune response, we further characterized our FcRn transgenic animals. Our analyses showed strong expression of the FcRn transgene in professional antigen presenting cells and we also found that overexpression of the FcRn significantly improves antigen presentation in case of antigen-IgG immune complexes. We have recently analyzed several key factors in the maturation of the immune response, including the structure of the spleen, number and structure of germinal centers, the level of T cell activation and the affinity of the generated antibodies. These results provide further insights of those mechanisms that are involved in the augmented humoral immune response in transgenic animals that overexpress FcRn.