Mouse κ light-chain recombination signal sequences mediate recombination more frequently than do those of λ light chain

Abstract

Immunoglobulin and T-cell receptor genes are somatically rearranged by site-specific recombination. Recombination signal sequences (RSS) have been identified as the major targeting element of this process. Recent reports demonstrate that differences in RSS affect the frequency of recombination, suggesting a role for RSS in the development of the B-cell repertoire. Examination of mouse light-chain RSS indicates that κ light-chain RSS consistently show a greater degree of similarity to a consensus sequence than do those of λ light chain. To determine whether this difference in natural RSS could affect the patterns of light-chain gene rearrangement and expression, we have constructed recombination substrates containing both a typical mouse κ RSS pair and a typical mouse λ RSS pair. Experiments using these substrates demonstrate that the κ RSS pair mediates recombination at a vastly higher frequency than does the λ RSS pair. This result argues that RSS differences may contribute significantly to the patterns of mouse immunoglobulin light-chain rearrangement, ultimately resulting in a high proportion of κ light chain relative to λ.