Abstract
This chapter discusses the various strategies used to introduce and express human immunoglobulin (Ig) heavy (H) and light (L) chain genes in transgenic animals and shows that a diverse human antibody repertoire can be obtained in a mouse background with silenced endogenous IgH and IgL chain loci. The use of large Ig loci permits hypermutation, class switching, and good expression levels. Because of the recent advances, several new technologies will be extensively used to produce high-affinity, fully human antibodies. Whole Ig loci will be routinely transferred in different species of animals, with their own antibody loci silenced by gene targeting or suppressed by selected breeding. The animals will be immunized and essentially provide highly specific, yet diverse human antibody repertoires. Besides producing high-affinity antibodies through recurring somatic hypermutation, extensive diversity will also be created in some translocus animals by gene conversion. Another approach may use targeted integration in a mouse Ig locus to replace not just endogenous C genes by human equivalents, and perhaps substitute many of the V genes by the insertion of artificial chromosomes. Cells expressing novel, high-affinity antibodies can be easily selected or identified using flow cytometry and cloning procedures. The chapter, in the end, discusses Mutator strains, which recombine and/or hypermutate introduced reporter genes with high efficiency, may provide a useful alternative to human antibody production in transgenic animals.
Published Version
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