| Autor: |
Wu, Cherry, Ranganath, Sheila, Gleason, Megan, Woodman, Barbara B., Borjeson, Tiffany M., Alt, Frederick W., Bassing, Craig H. |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 3/6/2007, Vol. 104 Issue 10, p4002-4007, 6p, 2 Diagrams, 1 Chart, 2 Graphs |
| Abstrakt: |
T cell antigen receptor (TCR)β V(D)J variable region exon assembly is ordered, with Dβ to Jβ rearrangements occurring before joining of Vβs to a DJβ complex. Germ-line V(D)J segments are flanked by recombination signal (RS) sequences, which consist of heptamers and nonamers separated by a spacer of 12 (12-RS) or 23 (23-RS) bp. V(D)J recombination is restricted by the 12/23 rule; joining occurs only between gene segments flanked by 12-RSs and 23-RSs. Vβ segments have 23-RSs and Jβ segments 12-RSs, which based on the 12/23 rule should allow direct joining. However, Vβ segments rearrange only to DJβ complexes and not Jβ segments, because of restrictions beyond 12/23 (B12/23) that make the Vβ23-RS incompatible with the Jβ12-RS. To determine whether direct Vβ to Jβ joining occurs if flanking RSs are B12/23 compatible, we generated mice whose lymphocytes contained replacement of the Vβ1412-RS with the 3′Dβ112-RS on a TCRβ allele lacking Dβ segments (the Jβ1M6 allele). Mice heterozygous for the Jβ1M6 allele had dramatically increased Vβ14+ thymocyte and T cell numbers and decreased numbers of cells expressing other Vβs. This altered Vβ repertoire resulted from direct Vβ14 to Jβ1 rearrangements on the Jβ1M6 allele. Mice harboring lymphocytes homozygous for Jβ1M6 allele developed normal thymocyte and T cell numbers with all expressing Vβ14. Our findings show that selective RS modifications enforce rearrangement of a specific Vβ gene segment and demonstrate the importance of B12/23 mechanisms for ensuring generation of diverse TCRβ repertoires. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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