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Analysis of the targeting of the hypermutational machinery and the impact of subsequent selection on the distribution of nucleotide changes in human V rearrangements
Author(s) -
Dörner Thomas,
Foster Sandra J.,
Brezinschek HansPeter,
Lipsky Peter E.,
Dörner Thomas,
Fustcr Sandra J.,
Brtzinschtk HonsPeltr,
Lipsky Peter E.
Publication year - 1998
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.1998.tb01439.x
Subject(s) - biology , selection (genetic algorithm) , gene , genetics , avidity , mutation , negative selection , positive selection , repertoire , distribution (mathematics) , antibody , genome , mathematical analysis , physics , mathematics , artificial intelligence , computer science , acoustics
Summary: 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 v H genes from individual human B cells provided an opportunity to examine the immediate impact of somatic hypermtitation without superimposed selective influences. Comparison with the frequency and distribution of mutations in the productively rearranged human V H genes permitted an estimate of the influences of subsequent selection.