Transgenic expression of bovine neonatal Fc receptor in mice boosts immune response and improves hybridoma production efficiency without any sign of autoimmunity

Abstract

The overexpression of the bovine neonatal Fc receptor (bFcRn) in transgenic (Tg) mice boosts humoral immune response with increased numbers of antigen-specific spleen cells and a potent humoral immune response against weakly immunogenic targets. One of the interesting questions surrounding this enhanced immune response is whether these Tg mice generate higher number of antigen-specific hybridomas. To address this question, we immunized these Tg mice and wild type (wt) controls with trinitrophenylated proteins, generated hybridomas and analyzed their numbers and specificities. We observed that Tg mice generated a 3-5 fold increase in antigen-specific IgG titers and had significantly larger spleens containing higher number of antigen-specific B cells and plasma cells, analyzed by ELISA and ELISPOT assays. Fusion of the isolated splenocytes with standard mouse myeloma cells (SP2/0-Ag14) resulted in a 2-4 fold elevation of hybridization frequency for the hapten, or carrier-specific IgG positive microcultures, in Tg mice compared to controls. In addition, as augmented immune reactivity leads to autoimmunity in some genetically modified mouse strains, we analyzed autoreactive antibody levels in serum samples derived from elderly bFcRn Tg mice by a protein chip assay. In contrast to the sample from the MRL/lpr mouse suffering from autoimmunity, we did not detect autoantibodies in bFcRn Tg mice or the wt controls. Based on these and our earlier data, we propose that Tg mice that overexpress bFcRn offer major advantages in monoclonal Ab production.