Immunoglobulin x light chain gene promoter and enhancer are not responsible for B-cell restricted gene rearrangement

Abstract

We have produced transgenic mice which synthesize chimeric mouse-rabbit immunoglobulin (Ig) x light chains following in vivo recombination of an injected unrearranged k gene. The exogenous gene construct contained a mouse germ-line k variable (Vk) gene segment, the mouse germ-line joining (Jx) locus including the enhancer, and the rabbit b9 constant (Ck) region. A high level of V-J recombination of the x transgene was observed in spleen of the transgenic mice. Surprisingly, a particularly high degree of variability in the exact site of recombination and the presence of non germ-line encoded nucleotides (N-regions) were found at the V-J junction of the rearranged x transgene. Furthermore, unlike endogenous x genes, rearrangement of the exogenous gene occurred in T-cells of the transgenic mice. These results show that additional sequences, other than the heptamer-nonamer signal sequences and the promoter and enhancer elements, are required to obtain stage and lineage specific regulation of Ig x light chain gene rearrangement in vivo