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Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density

B cells expressing high affinity antigen receptors are advantaged in germinal centers (GC), perhaps by increased acquisition of antigen for presentation to follicular helper T cells and improved T-cell help. In this model for affinity-dependent selection, the density of peptide/MHCII (pMHCII) comple...

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Autores principales: Yeh, Chen-Hao, Nojima, Takuya, Kuraoka, Masayuki, Kelsoe, Garnett
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834622/
https://www.ncbi.nlm.nih.gov/pubmed/29500348
http://dx.doi.org/10.1038/s41467-018-03382-x
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author Yeh, Chen-Hao
Nojima, Takuya
Kuraoka, Masayuki
Kelsoe, Garnett
author_facet Yeh, Chen-Hao
Nojima, Takuya
Kuraoka, Masayuki
Kelsoe, Garnett
author_sort Yeh, Chen-Hao
collection PubMed
description B cells expressing high affinity antigen receptors are advantaged in germinal centers (GC), perhaps by increased acquisition of antigen for presentation to follicular helper T cells and improved T-cell help. In this model for affinity-dependent selection, the density of peptide/MHCII (pMHCII) complexes on GC B cells is the primary determinant of selection. Here we show in chimeric mice populated by B cells differing only in their capacity to express MHCII (MHCII(+/+) and MHCII(+/−)) that GC selection is insensitive to halving pMHCII density. Alone, both B cell types generate identical humoral responses; in competition, MHCII(+/+) B cells are preferentially recruited to early GCs but this advantage does not persist once GCs are established. During GC responses, competing MHCII(+/+) and MHCII(+/−) GC B cells comparably accumulate mutations and have indistinguishable rates of affinity maturation. We conclude that B-cell selection by pMHCII density is stringent in the establishment of GCs, but relaxed during GC responses.
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spelling pubmed-58346222018-03-06 Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density Yeh, Chen-Hao Nojima, Takuya Kuraoka, Masayuki Kelsoe, Garnett Nat Commun Article B cells expressing high affinity antigen receptors are advantaged in germinal centers (GC), perhaps by increased acquisition of antigen for presentation to follicular helper T cells and improved T-cell help. In this model for affinity-dependent selection, the density of peptide/MHCII (pMHCII) complexes on GC B cells is the primary determinant of selection. Here we show in chimeric mice populated by B cells differing only in their capacity to express MHCII (MHCII(+/+) and MHCII(+/−)) that GC selection is insensitive to halving pMHCII density. Alone, both B cell types generate identical humoral responses; in competition, MHCII(+/+) B cells are preferentially recruited to early GCs but this advantage does not persist once GCs are established. During GC responses, competing MHCII(+/+) and MHCII(+/−) GC B cells comparably accumulate mutations and have indistinguishable rates of affinity maturation. We conclude that B-cell selection by pMHCII density is stringent in the establishment of GCs, but relaxed during GC responses. Nature Publishing Group UK 2018-03-02 /pmc/articles/PMC5834622/ /pubmed/29500348 http://dx.doi.org/10.1038/s41467-018-03382-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yeh, Chen-Hao
Nojima, Takuya
Kuraoka, Masayuki
Kelsoe, Garnett
Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density
title Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density
title_full Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density
title_fullStr Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density
title_full_unstemmed Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density
title_short Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density
title_sort germinal center entry not selection of b cells is controlled by peptide-mhcii complex density
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834622/
https://www.ncbi.nlm.nih.gov/pubmed/29500348
http://dx.doi.org/10.1038/s41467-018-03382-x
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