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In situ studies of the primary immune response to (4-hydroxy-3- nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells
In the murine spleen, germinal centers are the anatomic sites for antigen-driven hypermutation and selection of immunoglobulin (Ig) genes. To detail the kinetics of Ig mutation and selection, 178 VDJ sequences from 16 antigen-induced germinal centers were analyzed. Although germinal centers appeared...
Formato: | Texto |
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Lenguaje: | English |
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The Rockefeller University Press
1993
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191212/ https://www.ncbi.nlm.nih.gov/pubmed/8376935 |
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collection | PubMed |
description | In the murine spleen, germinal centers are the anatomic sites for antigen-driven hypermutation and selection of immunoglobulin (Ig) genes. To detail the kinetics of Ig mutation and selection, 178 VDJ sequences from 16 antigen-induced germinal centers were analyzed. Although germinal centers appeared by day 4, mutation was not observed in germinal center B cells until day 8 postimmunization; thereafter, point mutations favoring asymmetrical transversions accumulated until day 14. During this period, strong phenotypic selection on the mutant B lymphocytes was inferred from progressively biased distributions of mutations within the Ig variable region, the loss of crippling mutations, decreased relative clonal diversity, and increasingly restricted use of canonical gene segments. The period of most intense selection on germinal center B cell populations preceded significant levels of mutation and may represent a physiologically determined restriction on B cells permitted to enter the memory pathway. Noncanonical Ig genes recovered from germinal centers were mostly unmutated although they probably came from antigen-reactive cells. Together, these observations demonstrate that the germinal center microenvironment is rich and temporally complex but may not be constitutive for somatic hypermutation. |
format | Text |
id | pubmed-2191212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1993 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21912122008-04-16 In situ studies of the primary immune response to (4-hydroxy-3- nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells J Exp Med Articles In the murine spleen, germinal centers are the anatomic sites for antigen-driven hypermutation and selection of immunoglobulin (Ig) genes. To detail the kinetics of Ig mutation and selection, 178 VDJ sequences from 16 antigen-induced germinal centers were analyzed. Although germinal centers appeared by day 4, mutation was not observed in germinal center B cells until day 8 postimmunization; thereafter, point mutations favoring asymmetrical transversions accumulated until day 14. During this period, strong phenotypic selection on the mutant B lymphocytes was inferred from progressively biased distributions of mutations within the Ig variable region, the loss of crippling mutations, decreased relative clonal diversity, and increasingly restricted use of canonical gene segments. The period of most intense selection on germinal center B cell populations preceded significant levels of mutation and may represent a physiologically determined restriction on B cells permitted to enter the memory pathway. Noncanonical Ig genes recovered from germinal centers were mostly unmutated although they probably came from antigen-reactive cells. Together, these observations demonstrate that the germinal center microenvironment is rich and temporally complex but may not be constitutive for somatic hypermutation. The Rockefeller University Press 1993-10-01 /pmc/articles/PMC2191212/ /pubmed/8376935 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles In situ studies of the primary immune response to (4-hydroxy-3- nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells |
title | In situ studies of the primary immune response to (4-hydroxy-3- nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells |
title_full | In situ studies of the primary immune response to (4-hydroxy-3- nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells |
title_fullStr | In situ studies of the primary immune response to (4-hydroxy-3- nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells |
title_full_unstemmed | In situ studies of the primary immune response to (4-hydroxy-3- nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells |
title_short | In situ studies of the primary immune response to (4-hydroxy-3- nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells |
title_sort | in situ studies of the primary immune response to (4-hydroxy-3- nitrophenyl)acetyl. iii. the kinetics of v region mutation and selection in germinal center b cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191212/ https://www.ncbi.nlm.nih.gov/pubmed/8376935 |