Kd. Victor et Jd. Capra, AN APPARENTLY COMMON MECHANISM OF GENERATING ANTIBODY DIVERSITY - LENGTH VARIATION OF THE V(L)-J(L) JUNCTION, Molecular immunology, 31(1), 1994, pp. 39-46
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.