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

Some aspects of the work of our group on the human and mouse immunoglobulin kappa genes are reviewed. The human kappa locus contains a large duplication: a 600 kb C kappa -proximal copy with 40 V kappa genes is found in the close vicinity of a 440 kb C kappa -distal copy with 36 very similar, but not identical, V kappa genes. The chimpanzee has only the C kappa -proximal copy of the locus. The kappa kappa 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 V kappa genes and pseudogenes were localized and sequenced. In parallel to the elucidation of the structure of the kappa loci, the mechanisms of the V-J rearrangement, somatic hypermutation and kappa gene expression were studied. Various polymorphisms were detected in the human population and a number of haplotypes defined. in addition to the V kappa genes within the loci numerous V kappa orphons were localized on different chromosomes. Comparing the kappa 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 kappa 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.