Genomic organization of the sheep immunoglobulin JH segments and their contribution to heavy chain variable region diversity.

The sheep immunoglobulin heavy chain Igh-J locus has been characterized in order to determine the genomic organization of JH segments and their contribution to heavy chain diversity. The locus contains six segments, of which two are functional and four are apparently pseudogenes. These segments span a 1.8 kilobase (kb) region. The distance between JH-ps4 (the 3'-most segment) and the first domain of the mu-chain encoding constant gene is about 5 kb. The two functional JH segments have a standard upstream recombination signal sequence, including heptamer and nonamer sequences separated by a 22-23 nucleotide spacer, and end with a RNA donor splice site. These two segments possess all the characteristic JH invariant residues and are found in expressed mu heavy chain variable regions. The 5' functional JH1 segment is used in more than 90% of the cDNAs sequenced to date. The contribution of JH segment germline multiplicity to variable regions diversity appears therefore to be minimal. Comparison with other mammalian JH segments shows that all loci are very closely related and probably have evolved from a common ancestral locus.