LIGHT-CHAIN ISOTYPE REGULATION IN THE HORSE - CHARACTERIZATION OF IG-KAPPA GENES

Horse Ig kappa genes have been characterized to determine whether ther e may be a structural basis for the low level of kappa expression in t his species. The overall organization of the J kappa-C kappa locus is remarkably similar to that of the mouse and human loci. A single C kap pa exon is separated by 2.9 kb from five J kappa segments, four of whi ch seem functional and three of which are associated with canonical re combination signal sequences. A highly conserved intron enhancer was i dentified upstream of the C kappa exon and a single restriction fragme nt in horse genomic DNA hybridized strongly with the mouse downstream kappa enhancer. Germ-line and splenic cDNA V kappa sequences were char acterized and found to encode N-terminal amino acid sequences previous ly found by protein sequencing. Hybridization of horse genomic DNA wit h the horse V kappa-1 germ-line gene and a variety of mouse V kappa-re gion probes provided evidence for at least 20 V kappa gene segments. T he results indicate that the horse possesses a functional kappa locus with a complement of variable region gene segments potentially as larg e as that previously found at the lambda locus although the exact numb ers of functional variable region genes remains to be established for both loci. This finding suggests that the predominance of lambda-chain s in horse Ig may not be simply a result of a lack of functional kappa genes or of a disproportionate number of lambda vs kappa variable reg ion genes. The results are discussed in terms of various models of iso type regulation.