Sequence heterogeneity in Ig kappa transcripts from single B lymphocytes.
Individually amplified kappa cDNA molecules from single B lymphocytes revealed sequence heterogeneity and aberrantly spliced products. The nature and frequency of the base changes and their absence from similarly amplified beta2 microglobulin transcripts indicate that they were not derived by Taq polymerase misincorporations or by a general infidelity in RNA polymerase. The trinucleotide sequences in which the base changes occurred are disfavored targets of the somatic hypermutation mechanism that modifies antibody variable (V) region genes during immunity. Taken together with the observation that the transcript alterations were absent from the kappa Ig gene, this suggests that somatic mutations were acquired by the kappa gene and rapidly repaired following limited transcription. Preferential repair of mutations located in specific trinucleotide contexts could be the basis for some of the microsequence-specific bias in mutation frequencies observed in antibody V region genes.
Jena
P K
PK
Department of Immunology, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206, USA.
Liu
A H
AH
Smith
D S
DS
Aviszus
K
K
Wysocki
L J
LJ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair; D018076:DNA, Complementary / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D051379:Mice; D008805:Mice, Inbred A; D008969:Molecular Sequence Data; D017354:Point Mutation; D012313:RNA / Q000235:genetics; D012326:RNA Splicing; D014158:Transcription, Genetic
D017931:DNA Primers; D018076:DNA, Complementary; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D012313:RNA