Immunoglobulin gene ‘remnant’ DNA - implications for antibody gene recombination

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Abstract
Many immunoglobulin (Ig)-producinq cells retain the DNA that separates Ig variable (V) and constant (C) region genes in the germline. This “remnant” DNA must be moved during the recombination process that joins V and C genes via a joining (J) segment. We have analyzed remnant DNAs in several Ig-producing cell lines. The nucleotide sequences of kappa (κ) light chain remnant DNAs indicate close relationships to V-J joining. We find fused Vκ and Jκ recognition sequences in five remnant DNAs, suggesting reciprocal relationships to the fused Vκ and Jκ segments produced by V-J joining. However, of sixteen plasmacytoma remnant DNAs analyzed, all involve only recombination with Jκl. Thus, in most cell lines, remnant DNAs are not directly reciprocal to recombined κ-genes. On the other hand, our analyses of myelotnas do indicate indirect relationships between remnant DNAs and κ-genes. Our results suggest that multiple steps of DNA recombination occur during Ig-gene rearrangement. Because remnant DNA joining sites do not exhibit the flexibility that has been observed in Ig-gene V-J joining, our findings also suggest that the joining mechanism may involve endonuclease, exonuclease and liqase activities.