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Some aspects of the work of our group on the human and mouse immunoglobulin κ genes are reviewed. The human κ locus contains a large duplication: a 600 kb C-proximal copy with 40 Vκ genes is found in the close vicinity of a 440 kb Cκ-distal copy with 36 very similar, but not identical, Vκ genes. The chimpanzee has only the Cκ-proximal copy of the locus. The  locus of the mouse is close to 3.2 Mb in size, of which 3.1 Mb have been cloned in four contigs, leaving three small gaps of together about 90 kb; 140 Vκ genes and pseudogenes were localized and sequenced. In parallel to the elucidation of the structure of the κ loci, the mechanisms of the V-J rearrangement, somatic hypermutation and κ gene expression were studied. Various polymorphisms were detected in the human population and a number of haplotypes defined. In addition to the Vκ genes within the loci numerous Vκ orphons were localized on different chromosomes. Comparing the κ loci of different species allows some interesting conclusions as to the evolution of this multigene family. Finally our strategy of elucidating the structure and function of the κ loci, which has been termed a ‘cottage industry approach’, is discussed in relation to the large-scale genome analysis as pursued today using automated methods.

The Immunoglobulin κ Gene Families of Human and Mouse: a Cottage Industry Approach