Creation of valuable antibodies by an in vitro antibody generation system using a hypermutating B cell line

Naoki Kanayama, Kagefumi Todo, Masaki Magari, Hitoshi Ohmori

Research output: Contribution to journalArticle

Abstract

Monoclonal antibodies (mAb) have recently proven to be excellent biopharmaceutical agents. The generation of hybridomas from antigen-stimulated B cells has been a key technology for obtaining mAbs; however, it is a laborious and time-consuming process, and sometimes mAbs for molecules conserved between species are difficult to obtain because of immunological tolerance. Thus, it is of great importance to develop in vitro technologies for generating useful Abs as drug candidates. We have been attempting to develop a novel in vitro antibody generation system using a chicken B cell line DT40, which displays Abs and mutates Ig genes during culture, thereby generating a useful Ab library for screening mAbs. First, we generated an engineered cell line DT40-SW whose mutation machinery can be reversibly switched on and off. The Ab generation system using DT40-SW is useful in the following ways: (1) mAbs for various model antigens including antoantigens can be obtained from the DT40-SW Ab library that is free from immunological tolerance; (2) the switching device of the mutation machinery enables fixing desirable Ig mutants by stopping mutation; (3) by repeated culture and sorting of clones bearing higher affinity for target antigens, affinity maturation can be mimicked in vitro. We have also genetically improved DT40-SW cells for mutation efficiency and Ab production. The Ab generation system will be applicable for obtaining valuable Abs such as antitumor Abs.

Original languageEnglish
Pages (from-to)11-17
Number of pages7
JournalYakugaku Zasshi
Volume129
Issue number1
DOIs
Publication statusPublished - Jan 2009

Fingerprint

B-Lymphocytes
Cell Line
Mutation
Antibodies
Antigens
Libraries
Technology
Immunoglobulin Genes
Hybridomas
Chickens
Clone Cells
Monoclonal Antibodies
Equipment and Supplies
In Vitro Techniques
Pharmaceutical Preparations

Keywords

  • Affinity maturation
  • Antibody
  • DT40
  • Somatic mutation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Creation of valuable antibodies by an in vitro antibody generation system using a hypermutating B cell line. / Kanayama, Naoki; Todo, Kagefumi; Magari, Masaki; Ohmori, Hitoshi.

In: Yakugaku Zasshi, Vol. 129, No. 1, 01.2009, p. 11-17.

Research output: Contribution to journalArticle

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