V(D)J recombination: Born to be wild

Abstract

Vertebrates employ V(D)J recombination to generate diversity for an adaptive immune response. Born of a transposon, V(D)J recombination could conceivably cause more trouble than its worth. However, of the two steps required for transposon mobility (excision and integration) this particular transposon's integration step appears mostly blocked in cells. The employment of a transposon as raw material to develop adaptive immunity was thus a less-risky choice than it might have been … but is it completely risk-free?

Figure 1

V(D)J recombination. RAG1 and RAG2 direct chromosomal breakage at receptor gene loci. Nonhomologous end joining (NHEJ) resolves chromosome breaks to assemble a mature receptor gene (immunoglobulin or T cell receptor) and deleted extrachromosomal circle. Yellow rectangles denote receptor-coding DNA, and triangles denote recombination signals (RS).

Figure 2

Mechanisms for integration of the excised signal end fragment/putative transposon. Blue and black lines distinguish the putative transposon from its target site, and triangles denote recombination signals (RS). RAG-bound signal end complexes are noted by red oval. The features that distinguish the products of each mechanism from the others are noted at right. (A) Transposition. Gap repair to generate the flanking target site duplication is noted by arrows. (B) Intermolecular recombination (recombination in trans). (C) End donation (capture by an independently generated double strand break).

Figure 3

Hit-and-run Transposition. High RAG-mediated cleavage activity may keep the transposon mostly extrachromosomal (i), consistent with accumulation of linear fragment at the expense of circle (ii) and observed secondary recombinations after integration (iii).

Figure 4

Location of integrations mapped onto a mouse chromosome idiogram (http://www.pathology.washington.edu/research/cytopages/ideograms/mouse). Integrations are classified as in Figure 3 and Tables 1, 2.