Immunoglobulin kappa light chain gene promoter and enhancer are not responsible for B-cell restricted gene rearrangement.
We have produced transgenic mice which synthesize chimeric mouse-rabbit immunoglobulin (Ig) kappa light chains following in vivo recombination of an injected unrearranged kappa gene. The exogenous gene construct contained a mouse germ-line kappa variable (V kappa) gene segment, the mouse germ-line joining (J kappa) locus including the enhancer, and the rabbit b9 constant (C kappa) region. A high level of V-J recombination of the kappa 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 kappa transgene. Furthermore, unlike endogenous kappa 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 kappa light chain gene rearrangement in vivo.
Goodhardt
M
M
Unité de Génétique et Biochimie du Développement, LA CNRS 361, Institut Pasteur, Paris, France.
Babinet
C
C
Lutfalla
G
G
Kallenbach
S
S
Cavelier
P
P
Rougeon
F
F
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D013154:Spleen / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D014158:Transcription, Genetic
D007145:Immunoglobulin kappa-Chains