International Immunology Advance Access originally published online on January 10, 2005
International Immunology 2005 17(3):225-232; doi:10.1093/intimm/dxh202
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© 2005 The Japanese Society for Immunology
Chromosomal excision of TCR
chain genes is dispensable for 
ß T cell lineage commitment
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8118, St Louis, MO 63110, USA
Correspondence to: B. P. Sleckman; E-mail: sleckman{at}immunology.wustl.edu
TCRß, 
and 
chain genes are assembled and expressed in double-negative thymocytes prior to 
ß or T cell lineage commitment. Thus, cells committed to the ß T cell lineage can possess completely assembled TCR and/or TCR chain genes. However, these genes are not expressed. TCR chain gene expression may be silenced through the activity of a cis-acting silencer element. In the TCR/ locus, the TCR genes lie between the V and J gene segments, which rearrange by deletion. Moreover, V to J rearrangements occur on both alleles in essentially all developing ß T cells. Consequently, both TCR chain genes are excised from the chromosome and placed on extrachromosomal circles in mature ß T cells. It has been proposed that this excision process is important for silencing TCR gene expression and permitting ß T cell lineage commitment. A gene-targeting Cre–loxP strategy was used to invert a 75-kb region of the TCR/ locus encompassing all the J gene segments, generating the TCR/I allele. Initial V to J rearrangements on the TCR/I allele occur by inversion, resulting in chromosomal retention of TCR chain genes. These TCR chain genes can be productively rearranged and are expressed at levels similar to TCR chain genes in T cells. However, ß T cell development appears unperturbed in TCR/I/I mice. Thus, excision of TCR genes from the chromosome per se is not required for commitment of developing lymphocytes to the ß T cell lineage.
Keywords: antigen receptor, development, T lymphocyte, V(D)J recombination
Transmitting editor: D. Littman
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