NDLI: Mutation and selection during the secondary response to 2-phenyloxazolone.

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Mutation and selection during the secondary response to 2-phenyloxazolone.

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Mutation and selection during the secondary response to 2-phenyloxazolone.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Gherardi, E. Gupta, S. K. Milstein, C. Rada, C.
Description	Author Affiliation: Rada C ( Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.);
Abstract	The most characteristic feature of the mouse antibody response to the hapten 2-phenyloxazolone is the recurrent expression of the light-chain variable region Igk-VO chi 1 gene in its germ-line or mutated configuration. The analysis of somatic mutants of the Igk-VO chi 1 gene reported here indicates that, as found during the primary response, hypermutation is also activated during the secondary response. Somatic mutations in the Igk-VO chi 1 gene increased in sequences obtained at day 14 and day 21 in the primary response and again in the secondary response at days 3, 5, and 7. The ratio of replacement to silent mutations also increased, particularly between days 5 and 7, suggesting that a stage of negative selection operates on new somatic mutants generated in the secondary response. Most Igk-VO chi 1 mutants isolated in the secondary response had the features of selected memory clones (i.e., they carried mutations known to increase binding affinity for the hapten). However, some clones had chain-termination codons, and others had mutations predicting a nonfunctional light chain. At least three and possibly five of these clones also expressed the mutation characteristic of the memory response to 2-phenyloxazolone (His-34----Asn-34/Gln-34). We conclude that after a second antigenic challenge, new somatic variants, including some leading to the loss of antigen binding, are generated by hypermutation of cells derived from the memory pool.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	13
Volume Number	88
Language	English
Publisher	National Academy of Sciences
Publisher Date	1991-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antibody-Producing Cells Physiology B-Lymphocytes Immunoglobulin Kappa-Chains Genetics Immunologic Memory Oxazolone Analogs & Derivatives Amino Acid Sequence Animals Antibody Diversity Genes, Immunoglobulin Haptens Immunoglobulin Variable Region Mice Molecular Sequence Data Mutation Oligonucleotides Chemistry Immunology Polymerase Chain Reaction Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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