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Accelerating antibody discovery using transgenic animals overexpressing the neonatal Fc receptor as a result of augmented humoral immunity
Author(s) -
Cervenak Judit,
Kurrle Roland,
Kacskovics Imre
Publication year - 2015
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12364
Subject(s) - antibody , humoral immunity , biology , transgene , immunity , immunology , genetically modified mouse , immune system , receptor , virology , genetics , gene
Summary 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 ( GPCR s) 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.