Designer mice: the production of human antibody repertoires in transgenic animals
Brüggemann, M.; Davies, N.P.; Rosewell, I.R.
Year in Immunology 7: 33-40
1993
ISSN/ISBN: 0256-2308 PMID: 8372511 Document Number: 176
This review covers the immunogenicity of chimaeric antibodies, transfer of Ig genes to mice, somatic mutation in rearranged transgenes, Ig production by mouse hybridomas with human genes, the antibody repertoire in transgenic mice, and the introduction of yeast artificial chromosomes into embryonic stem cells of mice. Antibodies are composed of heavy (H) and light (L) chains which each consist of a variable (V) region and a constant (C) region. The heavy chain V region is made up from a V gene, a D (diversity) segment and a J (joining) segment. The V region. defines the specificity of an antibody and after DNA rearrangement from germline gene pools a VDJ-Cp transcript for the heavy chain and a VJ-CK transcript for the light chain is expressed. In addition, variability is generated by somatic mutation. The preparation of rodent monoclonal antibodies is an established procedure but there is a lack of specific and authentic human antibodies for therapeutic purposes. The production of human antibodies could be simplified by the availability of a mouse strain making human immunoglobulin (Ig). Current problems include the limitations of presently available genetic manipulation techniques, which make it difficult to introduce large parts of the human Ig locus into the mouse germline.
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