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International Immunology Advance Access published online on October 11, 2005
International Immunology, doi:10.1093/intimm/dxh333
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received September 2, 2005
Accepted September 14, 2005

Article

The positional effect of E{beta} on V{beta} genes of TCR{beta} chain in the ordered rearrangement and allelic exclusion

Daisuke Suzuki 1, Lili Wang 1, Makoto Senoo 2, and Sonoko Habu 1*

1 Department of Immunology, Tokai University School of Medicine, Bouseidai, Isehara, Kanagawa 259-1193, Japan
2 Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA

* To whom correspondence should be addressed.
Sonoko Habu, E-mail: sonoko{at}is.icc.u-tokai.ac.jp


  Abstract

In the TCR{beta} gene locus, the V{beta}, D{beta} and J{beta} gene segments are assembled in a tightly ordered manner. To investigate the positional effects of TCR{beta} enhancer (E{beta}) on the recombination processes of the V{beta} genes, we utilized {beta}LD mice lacking 70% of the TCR{beta} locus, leaving four V{beta} genes at the 5' side and, consequently, the V{beta}10 gene moves into the E{beta} regulatory region. In this mutant mouse, the V{beta}10 gene showed direct V{beta}-to-D{beta} and V{beta}-to-J{beta} recombination, although the D{beta}-to-J{beta} joining was still predominant. Interestingly, these two aberrant recombination processes were barely suppressed when {beta}LD mice were crossed with TCR{beta} transgenic mice, whereas V(D)J recombination of the V{beta}10 gene was sufficiently suppressed. These results suggest that the positional effects of E{beta} on the V{beta} genes may enable the recombination potential to increase prior to D{beta}-to-J{beta} joining and that such aberrant recombination may be free from allelic suppression.

Keywords: allelic exclusion; gene rearrangement; T cell receptors.
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