Accelerating antibody discovery using transgenic animals overexpressing the neonatal Fc receptor as a result of augmented humoral immunity

Judit Cervenak, Roland Kurrle, Imre Kacskovics

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

In recent years, there has been an increasing demand for the development of faster and more efficient technologies for the generation of monoclonal antibodies against challenging targets that are weakly immunogenic or available only in limited amounts. Typical classes of such targets are cell surface antigens such as G-protein related receptors (GPCRs) or ion channels. We have developed transgenic (Tg) mice and rabbits that overexpress the neonatal Fc receptor (FcRn), resulting in an augmented humoral immune response even if challenging antigens are used for immunization. The impressively enhanced FcRn-mediated immune reactions are characterized by improved IgG protection and enhanced antigen presentation leading to greater number of antigen-specific T-helper and B-cell activation in lymphoid organs. Notably, these animals do not show any sign of autoimmunity and can be efficiently bred. FcRn overexpression thus leads to a number of practical benefits for improved generation of monoclonal and polyclonal antibodies against multiple antigens, including weakly immunogenic epitopes or tiny amounts of proteins. This review summarizes our current understanding about the mechanisms by which FcRn overexpression leads to such a significantly enhanced humoral immune response.

Original languageEnglish
Pages (from-to)269-287
Number of pages19
JournalImmunological Reviews
Volume268
Issue number1
DOIs
Publication statusPublished - Nov 2015

Keywords

  • Antigen presentation
  • B-cell activation
  • Monoclonal and polyclonal antibody generation
  • Neonatal Fc receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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