Violations of the 12/23 rule at the mouse immunoglobulin kappa locus, including V kappa-V kappa rearrangement.
Classically, recombination between immunoglobulin gene segments uses a pair of recombination signal sequences (RSSs) with dissimilar spacers (the "12/23 rule"). Using a series of different genotyping assays, four different kinds of atypical rearrangements were identified at the murine kappa locus: (1) V kappa to V kappa, (2) J kappa to J kappa, (3) V kappa to iRS, a heptameric sequence found in the J kappa C kappa intron, and (4) a possible by-product of a rearrangement between a V kappa and the hypothetical 12-RSS side of a pre-existing signal joint. The novel V kappa-V kappa structure prompted further characterization. Sequence analysis of 14 different V kappa-V kappa rearrangements cloned from murine splenocytes and hybridomas revealed a V kappa 4 family member as one participant in 13 rearrangements, but no rearrangements contained two V kappa 4 genes. The V kappa 4 partner in the V kappa-V kappa rearrangement exhibited more trimming of nucleotides at the V kappa-V kappa junction. A signal joint derived from the inversional rearrangement of two neighboring V kappas was also recovered. These data suggest that the V kappa-V kappa structures arise via RAG-mediated, intrachromosomal recombination.
Vinocur
Jeffrey M
JM
University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, 405B Stellar Chance Labs, 422 Curie Blvd., Philadelphia, PA 19104, USA.
Fesnak
Andrew D
AD
Liu
Yang
Y
Charan
Deepshikha
D
Prak
Eline T Luning
ET
D000818:Animals; D001483:Base Sequence; D015321:Gene Rearrangement; D006825:Hybridomas / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D013154:Spleen / Q000276:immunology
D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains