Schematic of antibody H and L chain gene rearrangements. The full range of rearrangement products that can be generated at the H chain and L chain loci is shown. In the case of the heavy chain locus (IgH), there are three kinds of rearrangements: D to J rearrangements, V to DJ rearrangements and VH replacements (VHR). Note that all H chain rearrangements are deletional and that once a complete VDJ rearrangement has taken place, all of the D gene segments are consumed. During VH replacement, an upstream VH gene can invade into a pre-existing VDJ rearrangement via a cryptic heptamer (white triangle) that is located in the 3′ end of most VH genes. VH replacement has the potential to elongate the CDR3, because the 3′ end of the preceding VH gene is usually retained in the rearrangement. For the L chain loci (IgL), the kappa locus can undergo primary Vκ–Jκ rearrangement, leapfrogging rearrangement or recombining sequence (RS) deletional rearrangement. In the case of the leapfrogging rearrangement shown, rearrangement of an upstream Vκ gene to a downstream Jκ gene occurred by inversion. Inversional rearrangement retains the original Vκ–Jκ rearrangement on the chromosome in an inverted orientation. This remnant rearrangement is referred to as a reciprocal product. The κ locus can also undergo deletion by rearrangement to RS, a non-coding sequence that is approximately 25 kb downstream of Cκ. RS rearrangement can occur via the cryptic heptamer in the JC intron (i-RS) or by deletional rearrangement of a Vκ gene to RS. Both types of rearrangements inactivate the κ locus by deletion of the constant region exon, Cκ. Finally, lambda (λ) L chain rearrangement can occur. Most λ-expressing B cells have undergone RS deletion on one or both κ alleles. All of these rearrangements can be tracked and used to evaluate clonality, particularly in hybridoma studies (see text). Squares indicate exons, triangles recombination signal sequences, fused triangles represent signal joins and fused boxes indicate coding joins. Dashed lines indicate regions where recombining gene segments come together.
Philos Trans R Soc Lond B Biol Sci. 2015 September 5;370(1676):20140239.