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Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice

Nature Genetics volume 15, pages 146–156 (1997)Cite this article

A Correction to this article was published on 01 August 1997

Abstract

We constructed two megabase-sized YACs containing large contiguous fragments of the human heavy and kappa (κ) light chain immunoglobulin (Ig) loci in nearly germline configuration, including approximately 66 VH and 32 Vκ genes. We introduced these YACs into Ig-inactivated mice and observed human antibody production which closely resembled that seen in humans in all respects, including gene rearrangement, assembly, and repertoire. Diverse Ig gene usage together with somatic hypermutation enables the mice to generate high affinity fully human antibodies to multiple antigens, including human proteins. Our results underscore the importance of the large Ig fragments with multiple V genes for restoration of a normal humoral immune response. These mice are likely to be a valuable tool for the generation of therapeutic antibodies.

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Author notes

  1. Michael J. Mendez, Jac Luna, Hadi Abderrahim, Ford Kirschenbaum, Masato Noguchi, Douglas H. Smith, Atsushi Fukushima, Mitchell H. Finer & Krisztina M. Zsebo

    Present address: Cell Genesys, Inc., Foster City, California, 94404, USA

Authors and Affiliations

  1. Abgenix, Inc., 7601 Dumbarton Circle, Fremont, California, 94555, USA

    Larry L. Green, Jose R.F. Corvalan, Xiao-Chi Jia, Catherine E. Maynard-Currie, Xiao-dong Yang, Michael L. Gallo, Donna M. Louie, Doris V. Lee, Karen L. Erickson, Catherine M.-N. Roy, Joanna F. Hales, C. Geoffrey Davis & Aya Jakobovits

  2. JT Pharmaceutical Basic Research Laboratories, Yokohama, Japan

    Michael J. Mendez, Jac Luna, Hadi Abderrahim, Ford Kirschenbaum, Masato Noguchi, Douglas H. Smith, Atsushi Fukushima, Mitchell H. Finer & Krisztina M. Zsebo

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Mendez, M., Green, L., Corvalan, J. et al. Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice. Nat Genet 15, 146–156 (1997). https://doi.org/10.1038/ng0297-146

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