An apparently common mechanism of generating antibody diversity: length variation of the VL-JL junction.
The joining of various V, (D) and J gene segments during DNA rearrangement of the antigen receptor genes is one of the principle mechanisms responsible for the generation of antibody diversity. In the absence of N-segment variation, the structures of the coding joints formed during light chain rearrangement are thought to be less complex than their heavy chain counterparts. Consequently, the joining of the VL and JL gene segments during recombination account for all of the junctional diversity seen within the third complementarity determining region (CDR3). We generated kappa light chain transcripts from human fetal liver and peripheral blood lymphocytes and found that approximately one third exhibit a variation in the length of CDR3-independent of the JK gene segment utilized. Nucleotide sequence analysis reveals that many of the nucleotides at the VK-JK joint resulting in length variation of CDR3 are directly encoded by the germline VK and JK gene segments used in these transcripts. However, nearly 20% of the transcripts contain N-segment additions consistent with TdT-like activity. These 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 potential repertoire and thus contributes an additional means of generating diversity in the antibody molecule.
Victor
K D
KD
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-9048.
Capra
J D
JD
D000595:Amino Acid Sequence; D000916:Antibody Diversity / Q000235:genetics*; D001483:Base Sequence; D004247:DNA; D005312:Fetal Blood; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000235:genetics* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics* / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008969:Molecular Sequence Data; D012313:RNA / Q000235:genetics
D007144:Immunoglobulin J-Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D012313:RNA; D004247:DNA