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The Usage of Human IGHJ Genes Follows a Particular Non-random Selection: The Recombination Signal Sequence May Affect the Usage of Human IGHJ Genes
The formation of the B cell receptor (BCR) heavy chain variable region is derived from the germline V(D)J gene rearrangement according to the “12/23” rule and the “beyond 12/23” rule. The usage frequency of each V(D)J gene in the peripheral BCR repertoires is related to the initial recombination, se...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753069/ https://www.ncbi.nlm.nih.gov/pubmed/33363565 http://dx.doi.org/10.3389/fgene.2020.524413 |
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author | Shi, Bin Dong, Xiaoheng Ma, Qingqing Sun, Suhong Ma, Long Yu, Jiang Wang, Xiaomei Pan, Juan He, Xiaoyan Su, Danhua Yao, Xinsheng |
author_facet | Shi, Bin Dong, Xiaoheng Ma, Qingqing Sun, Suhong Ma, Long Yu, Jiang Wang, Xiaomei Pan, Juan He, Xiaoyan Su, Danhua Yao, Xinsheng |
author_sort | Shi, Bin |
collection | PubMed |
description | The formation of the B cell receptor (BCR) heavy chain variable region is derived from the germline V(D)J gene rearrangement according to the “12/23” rule and the “beyond 12/23” rule. The usage frequency of each V(D)J gene in the peripheral BCR repertoires is related to the initial recombination, self-tolerance selection, and the clonal proliferative response. However, their specific differences and possible mechanisms are still unknown. We analyzed in-frame and out-of-frame BCR-H repertoires from human samples with normal physiological and various pathological conditions by high-throughput sequencing. Our results showed that IGHJ gene frequency follows a similar pattern which is previously known, where IGHJ4 is used at high frequency (>40%), IGHJ6/IGHJ3/IGHJ5 is used at medium frequencies (10∼20%), and IGH2/IGHJ1 is used at low frequency (<4%) under whether normal physiological or various pathological conditions. However, our analysis of the recombination signal sequences suggested that the conserved non-amer and heptamer and certain 23 bp spacer length may affect the initial IGHD-IGHJ recombination, which results in different frequencies of IGHJ genes among the initial BCR-H repertoire. Based on this “initial repertoire,” we recommend that re-evaluation and further investigation are needed when analyzing the significance and mechanism of IGHJ gene frequency in self-tolerance selection and the clonal proliferative response. |
format | Online Article Text |
id | pubmed-7753069 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77530692020-12-23 The Usage of Human IGHJ Genes Follows a Particular Non-random Selection: The Recombination Signal Sequence May Affect the Usage of Human IGHJ Genes Shi, Bin Dong, Xiaoheng Ma, Qingqing Sun, Suhong Ma, Long Yu, Jiang Wang, Xiaomei Pan, Juan He, Xiaoyan Su, Danhua Yao, Xinsheng Front Genet Genetics The formation of the B cell receptor (BCR) heavy chain variable region is derived from the germline V(D)J gene rearrangement according to the “12/23” rule and the “beyond 12/23” rule. The usage frequency of each V(D)J gene in the peripheral BCR repertoires is related to the initial recombination, self-tolerance selection, and the clonal proliferative response. However, their specific differences and possible mechanisms are still unknown. We analyzed in-frame and out-of-frame BCR-H repertoires from human samples with normal physiological and various pathological conditions by high-throughput sequencing. Our results showed that IGHJ gene frequency follows a similar pattern which is previously known, where IGHJ4 is used at high frequency (>40%), IGHJ6/IGHJ3/IGHJ5 is used at medium frequencies (10∼20%), and IGH2/IGHJ1 is used at low frequency (<4%) under whether normal physiological or various pathological conditions. However, our analysis of the recombination signal sequences suggested that the conserved non-amer and heptamer and certain 23 bp spacer length may affect the initial IGHD-IGHJ recombination, which results in different frequencies of IGHJ genes among the initial BCR-H repertoire. Based on this “initial repertoire,” we recommend that re-evaluation and further investigation are needed when analyzing the significance and mechanism of IGHJ gene frequency in self-tolerance selection and the clonal proliferative response. Frontiers Media S.A. 2020-12-08 /pmc/articles/PMC7753069/ /pubmed/33363565 http://dx.doi.org/10.3389/fgene.2020.524413 Text en Copyright © 2020 Shi, Dong, Ma, Sun, Ma, Yu, Wang, Pan, He, Su and Yao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Shi, Bin Dong, Xiaoheng Ma, Qingqing Sun, Suhong Ma, Long Yu, Jiang Wang, Xiaomei Pan, Juan He, Xiaoyan Su, Danhua Yao, Xinsheng The Usage of Human IGHJ Genes Follows a Particular Non-random Selection: The Recombination Signal Sequence May Affect the Usage of Human IGHJ Genes |
title | The Usage of Human IGHJ Genes Follows a Particular Non-random Selection: The Recombination Signal Sequence May Affect the Usage of Human IGHJ Genes |
title_full | The Usage of Human IGHJ Genes Follows a Particular Non-random Selection: The Recombination Signal Sequence May Affect the Usage of Human IGHJ Genes |
title_fullStr | The Usage of Human IGHJ Genes Follows a Particular Non-random Selection: The Recombination Signal Sequence May Affect the Usage of Human IGHJ Genes |
title_full_unstemmed | The Usage of Human IGHJ Genes Follows a Particular Non-random Selection: The Recombination Signal Sequence May Affect the Usage of Human IGHJ Genes |
title_short | The Usage of Human IGHJ Genes Follows a Particular Non-random Selection: The Recombination Signal Sequence May Affect the Usage of Human IGHJ Genes |
title_sort | usage of human ighj genes follows a particular non-random selection: the recombination signal sequence may affect the usage of human ighj genes |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753069/ https://www.ncbi.nlm.nih.gov/pubmed/33363565 http://dx.doi.org/10.3389/fgene.2020.524413 |
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