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Defects in Germinal Center Selection in SLE
Germinal centers (GCs) are the primary site at which clonal expansion and affinity maturation of B cells occur. B cells encounter antigen and receive T cell help in the GC light zone (LZ) and then migrate to the dark zone where they proliferate and undergo somatic mutation before cycling back to the...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536402/ https://www.ncbi.nlm.nih.gov/pubmed/26322049 http://dx.doi.org/10.3389/fimmu.2015.00425 |
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author | Woods, Megan Zou, Yong-Rui Davidson, Anne |
author_facet | Woods, Megan Zou, Yong-Rui Davidson, Anne |
author_sort | Woods, Megan |
collection | PubMed |
description | Germinal centers (GCs) are the primary site at which clonal expansion and affinity maturation of B cells occur. B cells encounter antigen and receive T cell help in the GC light zone (LZ) and then migrate to the dark zone where they proliferate and undergo somatic mutation before cycling back to the LZ for further rounds of selection. Tolerance to autoantigens is frequently lost de novo as GC B cells undergo class switching and somatic mutation. This loss of tolerance is regulated by a variety of mechanisms including cell death, failure to compete for T cell help, and failure to differentiate into effector cells. Systemic lupus erythematosus (SLE) is characterized by loss of tolerance to nucleic acid antigens. While defects in tolerance occur in the naïve repertoire of SLE patients, pathogenic autoantibodies also arise in the GC by somatic mutation from non-autoreactive precursors. Several B cell defects contribute to the loss of GC tolerance in SLE, including polymorphisms of genes encoded by the Sle1 locus, excess TLR7 signaling, defects in FcRIIB expression, or defects of B cell apoptosis. Extrinsic soluble factors, such as Type-1 IFN and B cell-activating factor, or an increased number of T follicular helper cells in the GC also alter B cell-negative selection. Finally, defects in clearance of apoptotic debris within the GC result in BCR-mediated internalization of nucleic acid containing material and stimulation of autoantibody production by endosomal TLR-driven mechanisms. |
format | Online Article Text |
id | pubmed-4536402 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-45364022015-08-28 Defects in Germinal Center Selection in SLE Woods, Megan Zou, Yong-Rui Davidson, Anne Front Immunol Immunology Germinal centers (GCs) are the primary site at which clonal expansion and affinity maturation of B cells occur. B cells encounter antigen and receive T cell help in the GC light zone (LZ) and then migrate to the dark zone where they proliferate and undergo somatic mutation before cycling back to the LZ for further rounds of selection. Tolerance to autoantigens is frequently lost de novo as GC B cells undergo class switching and somatic mutation. This loss of tolerance is regulated by a variety of mechanisms including cell death, failure to compete for T cell help, and failure to differentiate into effector cells. Systemic lupus erythematosus (SLE) is characterized by loss of tolerance to nucleic acid antigens. While defects in tolerance occur in the naïve repertoire of SLE patients, pathogenic autoantibodies also arise in the GC by somatic mutation from non-autoreactive precursors. Several B cell defects contribute to the loss of GC tolerance in SLE, including polymorphisms of genes encoded by the Sle1 locus, excess TLR7 signaling, defects in FcRIIB expression, or defects of B cell apoptosis. Extrinsic soluble factors, such as Type-1 IFN and B cell-activating factor, or an increased number of T follicular helper cells in the GC also alter B cell-negative selection. Finally, defects in clearance of apoptotic debris within the GC result in BCR-mediated internalization of nucleic acid containing material and stimulation of autoantibody production by endosomal TLR-driven mechanisms. Frontiers Media S.A. 2015-08-14 /pmc/articles/PMC4536402/ /pubmed/26322049 http://dx.doi.org/10.3389/fimmu.2015.00425 Text en Copyright © 2015 Woods, Zou and Davidson. 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) or licensor 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 | Immunology Woods, Megan Zou, Yong-Rui Davidson, Anne Defects in Germinal Center Selection in SLE |
title | Defects in Germinal Center Selection in SLE |
title_full | Defects in Germinal Center Selection in SLE |
title_fullStr | Defects in Germinal Center Selection in SLE |
title_full_unstemmed | Defects in Germinal Center Selection in SLE |
title_short | Defects in Germinal Center Selection in SLE |
title_sort | defects in germinal center selection in sle |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536402/ https://www.ncbi.nlm.nih.gov/pubmed/26322049 http://dx.doi.org/10.3389/fimmu.2015.00425 |
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