Some aspects of the work of our group on the human and mouse immunoglobulin genes are reviewed. The human locus contains a large duplication: a 600 kb C -proximal copy with 40 V genes is found in the close vicinity of a 440 kb C -distal copy with 36 very similar, but not identical, V genes. The chimpanzee has only the C -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 V genes and pseudogenes were localized and sequenced. In parallel to the elucidation of the structure of the loci, the mechanisms of the V-J rearrangement, somatic hypermutation and gene expression were studied. Various polymorphisms were detected in the human population and a number of haplotypes defined. In addition to the V genes within the loci numerous V orphons were localized on different chromosomes. Comparing the 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 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. Key words: Contigs / Human / Immunoglobulin locus / Mouse.The genes and loci of the immunoglobulin heavy and light chains have been reviewed by Honjo and Alt (1995) and by Max (1999). A wealth of structural and functional data is also available on the Internet (Immunoglobulin gene databases, 1999).
Work on Immunoglobulin Genes in MunichIn our laboratory the work on immunoglobulin genes started in the late '70s with experiments in which the chromatin structure of expressed genes in mouse myelomas was compared to the chromatin structure of the corresponding silent genes in mouse liver. In the following years both chromatin and immunoglobulin gene projects were pursued in our laboratory, but it turned out that the chromatin work was slow-moving and not very informative. On the other hand, at that time Tonegawa discovered the recombination of variable, joining and constant (V, J, C) gene segments and many researchers, including us, were intrigued by the new possibilities of cloning and analyzing mammalian genes. We found the reciprocal recombination products, now called signal joints (Steinmetz et al., 1980), contributed to the understanding of somatic mutations (Pech et al., 1981) and defined the immunoglobulin gene promoter (Falkner and Zachau, 1984). The last chromatin project in our lab came to an end in 1984. A few years later chromatin research picked up momentum worldwide again, but by then we were fully engaged in work on immunoglobulin genes and did not return to chromatin.After working on immunoglobulin genes for a few years we felt that in order to understand certain functional and mechanistic aspects, we should know all V, J and C genes in at least one of the loci. Therefore in 1982 we embarked on an attempt to clone all human immunoglobulin V genes. 12 year...