AN APPARENTLY COMMON MECHANISM OF GENERATING ANTIBODY DIVERSITY - LENGTH VARIATION OF THE V(L)-J(L) JUNCTION

The joining of various V, (D) and J gene segments during DNA rearrange ment of the antigen receptor genes is one of the principle mechanisms responsible for the generation of antibody diversity. In the absence o f N-segment variation, the structures of the coding joints formed duri ng light chain rearrangement are thought to be less complex than their heavy chain counterparts. Consequently, the joining of the V(L) and J (L) gene segments during recombination account for all of the junction al diversity seen within the third complementarity determining region (CDR3). We generated kappa light chain transcripts from human fetal li ver and peripheral blood lymphocytes and found that approximately one third exhibit a variation in the length of CDR3-independent of the J(K ) gene segment utilized. Nucleotide sequence analysis reveals that man y of the nucleotides at the V(K)-J(K) joint resulting in length variat ion of CDR3 are directly encoded by the germline V(K) and J(K) gene se gments used in these transcripts. However, nearly 20% of the transcrip ts contain N-segment additions consistent with TdT-like activity. Thes e observations suggest that TdT or an analogous enzyme must be active in a significant percentage of human B-lymphocytes during light chain rearrangement. Length variation in light chain CDR3 expands the potent ial repertoire and thus contributes an additional means of generating diversity in the antibody molecule.