Analysis of the targeting of the hypermutational machinery and the impact of subsequent selection on the distribution of nucleotide changes in human VHDJH rearrangements.
B cells are unique in that they generate and tolerate a high rate of mutations in their antigen receptor genes and employ these mutations as a basis of avidity maturation. The precise role of the mutational machinery versus subsequent selection in determining the frequency and distribution of mutations has not been fully analyzed. To address these issues, the influence of the intrinsic mutational machinery and subsequent selection on the frequency and distribution of mutations in the expressed human immunoglobulin repertoire was analyzed. Analysis of non-productively rearranged VH genes from individual human B cells provided an opportunity to examine the immediate impact of somatic hypermutation without superimposed selective influences. Comparison with the frequency and distribution of mutations in the productively rearranged human VH genes permitted an estimate of the influences of subsequent selection.
Dörner
T
T
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas 75235-8884, USA.
Foster
S J
SJ
Brezinschek
H P
HP
Lipsky
P E
PE
D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D003062:Codon; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007144:Immunoglobulin J-Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007138:Immunoglobulin delta-Chains / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation
D003062:Codon; D007143:Immunoglobulin Heavy Chains; D007144:Immunoglobulin J-Chains; D007135:Immunoglobulin Variable Region; D007138:Immunoglobulin delta-Chains