ISSN:
1600-065X
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Summary: Assembly of antigen receptor genes is regulated in several important contexts during lymphocyte development. This regulation occurs through modulation of gene segment accessibility to the V(D)J recombinase and/or at the level of the recombination reaction due, in part, to constraints imposed by recombination signal (RS) sequences. RSs are composed of conserved heptamer and nonamer sequences that flank relatively non-conserved spacer sequences of either 12 or 23 base pairs. Recombination occurs only between RSs of dissimilar spacer lengths, a restriction known as the 12/23 rule. Recently, we have shown that RSs can impose significant constraints on antigen receptor gene assembly beyond enforcing the 12/23 rule. This restriction, termed B12/23, was revealed by analysis of T-cell receptor β (TCRβ) locus rearrangements, where Dβ 12RSs and not Jβ 12RSs are capable of efficiently targeting Vβ 23RSs' rearrangement. The B12/23 restriction occurs at or prior to the DNA-cleavage step of the V(D)J recombination reaction, relies on features of the Dβ 12RSs and Vβ 23RSs, and is not absolutely dependent on lymphoid-specific factors other than the recombinase-activating gene-1 (RAG-1) and RAG-2 proteins. By preserving Dβ gene segment utilization, the B12/23 restriction is required, at a minimum, for the generation of a diverse repertoire of TCRβ chains.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.0105-2896.2004.00156.x
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