Dramatically increased rearrangement and peripheral representation of Vbeta14 driven by the 3'Dbeta1 recombination signal sequence.
V(D)J recombination is targeted by short recombination signal (RS) sequences that are relatively conserved but exhibit natural sequence variations. To evaluate the potential of RS sequence variations to determine the primary and peripheral TCRbeta repertoire, we generated mice containing specific replacement of the endogenous Vbeta14 RS with the 3'Dbeta1 RS (Vbeta14/3'DbetaRS). These mice exhibited a dramatic increase in Vbeta14(+) thymocyte numbers at the expense of thymocytes expressing other Vbetas. In addition, the percentage of peripheral Vbeta14(+) alphabeta T lymphocytes was similarly increased. Strikingly, this altered Vbeta repertoire resulted predominantly from a higher relative level of primary Vbeta14/3'DbetaRS rearrangement to DbetaJbeta complexes, despite the ability of the 3'Dbeta1 RS to break B12/23 restriction and allow direct rearrangement of Vbeta14/3'DbetaRS to Jbeta segments.
Wu
Cherry
C
Howard Hughes Medical Institute, The Children's Hospital, Harvard University Medical School, Boston, MA 02115, USA.
Bassing
Craig H
CH
Jung
David
D
Woodman
Barbara B
BB
Foy
Dan
D
Alt
Frederick W
FW
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D018390:Gene Targeting; D019674:Genes, T-Cell Receptor beta; D005822:Genetic Vectors; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA