Immunoglobulin gene 'remnant' DNA--implications for antibody gene recombination.
Many immunoglobulin (Ig)-producing 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 (kappa) light chain remnant DNAs indicate close relationships to V-J joining. We find fused V kappa and J kappa recognition sequences in five remnant DNAs, suggesting reciprocal relationships to the fused V kappa and J kappa segments produced by V-J joining. However, of sixteen plasmacytoma remnant DNAs analyzed, all involve only recombination with J kappa l. Thus, in most cell lines, remnant DNAs are not directly reciprocal to recombined kappa-genes. On the other hand, our analyses of some myelomas do indicate indirect relationships between remnant DNAs and kappa-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 ligase activities.
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D004262:DNA Restriction Enzymes; D005796:Genes; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics*; D008223:Lymphoma / Q000276:immunology; D051379:Mice; D010954:Plasmacytoma / Q000276:immunology
D007127:Immunoglobulin Constant Regions; D007144:Immunoglobulin J-Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007136:Immunoglobulins; D004262:DNA Restriction Enzymes