COMPOSITE EXON STRUCTURE OF AN UNUSUAL IG LAMBDA-LIKE GENE LOCATED ATHUMAN 22Q11 POSITION

The surrogate light chain, composed of the VpreB and the lambda-like p roteins, plays a critical role in controlling the early stages of B ly mphocyte development. The lambda-like locus, located on the q11.2-q11. 3 region of human Chromosome (Chr) 22, contains three genes (14.1 F la mbda-1, and 16.1) among which only the 14.1 is functional. This gene c ontains three exons, whereas the others lack exon 1. We have isolated in fetal liver a transcript of the F lambda-1 gene that contains the e xon 3 sequence and a long non-Ig related sequence upstream. We show th at this sequence resulted from the splicing of three new exons located telomeric to the F lambda-1 gene, highly homologous to beta-glucuroni dase exon 11 (Chr 7), to the ABR exon 8 (Chr 17), and to an Expressed Sequence Tag (EST), respectively. We also show that this chimeric tran script is ex pressed in cells or tissues from various origins. This co mposite gene structure appears to be a new example of human genome fle xibility, which can be explained by mechanisms such as exon shuffling and which results in the emergence of new transcription units inserted in regions involved in translocations.