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Molecular genetics at the T-cell receptor beta locus: insights into the regulation of V(D)J recombination
Marie Bonnet1, Pierre Ferrier, Salvatore Spicuglia
1Centre d'Immunologie de Marseille-Luminy, Université d'Aix Marseille, CNRS, UMR 6102, Inserm, U 631, Marseille, France.
The V(D)J recombination machinery assembles antigen receptor genes from germline V, D and J segments duringlymphocyte development. In alphabetaT cells, this leads to the production of the T-cell receptor (TCR) alpha and beta chains. Notably, V(D)J recombination at the Tcrb locus is tightly controlled at various levels, including cell-type and stage specificities, intralocus ordering and allelic exclusion. Although many of these controls are partly mediated at the level of genomic accessibility to the V(D)J recombinase, recent studies have uncovered novel mechanisms that are also likely to contribute to the developmental regulation of Tcrb gene rearrangement events. In this chapter, we summarize our current knowledge and highlight unanswered questions regarding the regulation of V(D)J recombination at the Tcrb locus, placing emphasis on mouse transgenesis and gene-targeting approaches.
The V(D)J recombination machinery assembles antigen receptor genes from germline V, D and J segments duringlymphocyte development. In alphabetaT cells, this leads to the production of the T-cell receptor (TCR) alpha and beta chains. Notably, V(D)J recombination at the Tcrb locus is tightly controlled at various levels, including cell-type and stage specificities, intralocus ordering and allelic exclusion. Although many of these controls are partly mediated at the level of genomic accessibility to the V(D)J recombinase, recent studies have uncovered novel mechanisms that are also likely to contribute to the developmental regulation of Tcrb gene rearrangement events. In this chapter, we summarize our current knowledge and highlight unanswered questions regarding the regulation of V(D)J recombination at the Tcrb locus, placing emphasis on mouse transgenesis and gene-targeting approaches.
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