Mapping of the duplicated rabbit immunoglobulin χ light chain locus

Abstract

The rabbit has two isotypic forms of the immunoglobulin χ light chain, K1 and K2, which probably arose by duplication. In the normal rabbit, only traces of K2 light chains are produced. However, K2 levels are elevated in allotype-suppressed rabbits and in the Basilea strain which does not produce K1 because of a K1 mRNA splice site mutation. Previous cloning and sequencing showed that each isotype has its own set of J_χ genes but it was not known whether the two isotypes utilize shared or separate sets of V_χ genes. In addition, although genetic linkage of allotypes associated with the K1 and K2 genes has been demonstrated, physical linkage had not been previously demonstrated by overlapping cosmid or phage clones. We used pulsed field and transverse alternating field electrophoresis to obtain megabase maps and to estimate the size of the duplication of the rabbit χ light chain locus. We found that the two C_χ genes are about 1 megabase apart. One explanation for the poor expression of K2, could be great physical distance from V_χ genes. However, we found that there are V_χ, J_χ and C_χ2 genes within a ∼ 105-kb fragment. Thus, physical distance of V_χ from C_χ2 may not be the basis for poor K2 expression.