Figure 4. Recombination events associated with receptor editing on the immunoglobulin κ locus can silence or alter gene expression.

The top line of the figure shows the germline configuration of gene segments in the human immunoglobulin κ (Igκ) locus, with variable (V) and joining (J) elements flanked by recombination signal sequences (RSSs). Also shown is the κ deleting element (kde). The first rearrangement on a locus is known as the primary rearrangement. Secondary rearrangement can silence the primary rearrangement; for example, in this case, V2 rearrangement to a downstream J element replaces the V4–J join. Note that some Vκ genes rearrange by inversion rather than excision of intervening DNA (not shown). When they are in-frame, secondary rearrangements can replace one functional V region with another. However, like all immunoglobulin gene rearrangements, these rearrangements are often non-functional and so can silence κ light-chain protein expression rather than replace it. Out-of-frame primary rearrangements can similarly be displaced by secondary rearrangements. Even loci that have ‘used up’ the J elements (arrow) can silence the locus by subsequent kde recombination (bottom line). The kde has no coding function, but behaves as a non-functional, but rearrangeable, J element, leading to deletion of the constant (C) region and silencing of the locus. Such rearrangements are often found in cells expressing λ light chains. The λ locus in humans has a similar organization, although a kde-like element has not been identified.