Mouse kappa light-chain recombination signal sequences mediate recombination more frequently than do those of lambda light chain.
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 kappa light-chain RSS consistently show a greater degree of similarity to a consensus sequence than do those of lambda 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 kappa RSS pair and a typical mouse lambda RSS pair. Experiments using these substrates demonstrate that the kappa RSS pair mediates recombination at a vastly higher frequency than does the lambda 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 kappa light chain relative to lambda.
Ramsden
D A
DA
Department of Immunology, University of Toronto, Ontario, Canada.
Wu
G E
GE
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004254:DNA Nucleotidyltransferases / Q000378:metabolism*; D015321:Gene Rearrangement; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D021382:Protein Sorting Signals / Q000235:genetics*; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid; D045567:VDJ Recombinases
D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D009838:Oligodeoxyribonucleotides; D021382:Protein Sorting Signals; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases