FcRn overexpression in mice results in potent humoral response against weakly immunogenic antigen

Attila Végh, Judit Cervenak, István Jankovics, I. Kacskovics

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The neonatal Fc receptor (FcRn) regulates IgG and albumin homeostasis, mediates maternal IgG transport, is active in phagocytosis and delivers antigen for presentation. We have previously shown that transgenic (tg) mice that have been created to overexpress bovine FcRn (bFcRn) demonstrate increased half-life of mouse IgG, significantly increased antigenspecific IgG in serum and augmented expansion of antigen-specific B cells and plasma cells after immunization. One of the interesting questions surrounding this enhanced immune response is whether these tg mice could effectively induce immune response to weakly immunogenic antigens. To address this question, we immunized these bFcRn tg mice with a conserved hemagglutinin subunit 2 (HA2)-based synthetic peptide that was recently found to be effectively targeted by neutralizing antibodies. Using an ELISA system, we found that, whereas wild-type mice showed a weak immune response and developed only a de minimis amount of antibody against the epitope, FcRn overexpressing animals mounted a robust reaction expressed in specific antibody titers on day 28 that continued to rise through day 50. Consistent with our previous data, the enhanced immune response resulting from the FcRn overexpression was also associated with a substantial increase in the number of spleen derived B cells, dendritic cells, granulocytes and plasma cells. Based on this evidence, we propose that tg mice that overexpress bFcRn offer major advantages in monoclonal antibody production because the tg mice would allow the generation of antibodies (hybridomas) to weakly immunogenic antigens that otherwise would be diffi cult or even impossible to make.

Original languageEnglish
Pages (from-to)176-183
Number of pages8
JournalmAbs
Volume3
Issue number2
DOIs
Publication statusPublished - Jan 1 2011

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Keywords

  • Immunogenicity
  • Influenza
  • Monoclonal antibody
  • Neonatal Fc receptor (FcRn)
  • Transgenic mouse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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