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Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells
Valency requirements for B cell activation upon antigen encounter are poorly understood. OB1 transnuclear B cells express an IgG1 B cell receptor (BCR) specific for ovalbumin (OVA), the epitope of which can be mimicked using short synthetic peptides to allow antigen-specific engagement of the BCR. B...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920557/ https://www.ncbi.nlm.nih.gov/pubmed/24493799 http://dx.doi.org/10.1084/jem.20131603 |
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author | Avalos, Ana M. Bilate, Angelina M. Witte, Martin D. Tai, Albert K. He, Jiang Frushicheva, Maria P. Thill, Peter D. Meyer-Wentrup, Friederike Theile, Christopher S. Chakraborty, Arup K. Zhuang, Xiaowei Ploegh, Hidde L. |
author_facet | Avalos, Ana M. Bilate, Angelina M. Witte, Martin D. Tai, Albert K. He, Jiang Frushicheva, Maria P. Thill, Peter D. Meyer-Wentrup, Friederike Theile, Christopher S. Chakraborty, Arup K. Zhuang, Xiaowei Ploegh, Hidde L. |
author_sort | Avalos, Ana M. |
collection | PubMed |
description | Valency requirements for B cell activation upon antigen encounter are poorly understood. OB1 transnuclear B cells express an IgG1 B cell receptor (BCR) specific for ovalbumin (OVA), the epitope of which can be mimicked using short synthetic peptides to allow antigen-specific engagement of the BCR. By altering length and valency of epitope-bearing synthetic peptides, we examined the properties of ligands required for optimal OB1 B cell activation. Monovalent engagement of the BCR with an epitope-bearing 17-mer synthetic peptide readily activated OB1 B cells. Dimers of the minimal peptide epitope oriented in an N to N configuration were more stimulatory than their C to C counterparts. Although shorter length correlated with less activation, a monomeric 8-mer peptide epitope behaved as a weak agonist that blocked responses to cell-bound peptide antigen, a blockade which could not be reversed by CD40 ligation. The 8-mer not only delivered a suboptimal signal, which blocked subsequent responses to OVA, anti-IgG, and anti-kappa, but also competed for binding with OVA. Our results show that fine-tuning of BCR-ligand recognition can lead to B cell nonresponsiveness, activation, or inhibition. |
format | Online Article Text |
id | pubmed-3920557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-39205572014-08-10 Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells Avalos, Ana M. Bilate, Angelina M. Witte, Martin D. Tai, Albert K. He, Jiang Frushicheva, Maria P. Thill, Peter D. Meyer-Wentrup, Friederike Theile, Christopher S. Chakraborty, Arup K. Zhuang, Xiaowei Ploegh, Hidde L. J Exp Med Article Valency requirements for B cell activation upon antigen encounter are poorly understood. OB1 transnuclear B cells express an IgG1 B cell receptor (BCR) specific for ovalbumin (OVA), the epitope of which can be mimicked using short synthetic peptides to allow antigen-specific engagement of the BCR. By altering length and valency of epitope-bearing synthetic peptides, we examined the properties of ligands required for optimal OB1 B cell activation. Monovalent engagement of the BCR with an epitope-bearing 17-mer synthetic peptide readily activated OB1 B cells. Dimers of the minimal peptide epitope oriented in an N to N configuration were more stimulatory than their C to C counterparts. Although shorter length correlated with less activation, a monomeric 8-mer peptide epitope behaved as a weak agonist that blocked responses to cell-bound peptide antigen, a blockade which could not be reversed by CD40 ligation. The 8-mer not only delivered a suboptimal signal, which blocked subsequent responses to OVA, anti-IgG, and anti-kappa, but also competed for binding with OVA. Our results show that fine-tuning of BCR-ligand recognition can lead to B cell nonresponsiveness, activation, or inhibition. The Rockefeller University Press 2014-02-10 /pmc/articles/PMC3920557/ /pubmed/24493799 http://dx.doi.org/10.1084/jem.20131603 Text en © 2014 Avalos et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Avalos, Ana M. Bilate, Angelina M. Witte, Martin D. Tai, Albert K. He, Jiang Frushicheva, Maria P. Thill, Peter D. Meyer-Wentrup, Friederike Theile, Christopher S. Chakraborty, Arup K. Zhuang, Xiaowei Ploegh, Hidde L. Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells |
title | Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells |
title_full | Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells |
title_fullStr | Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells |
title_full_unstemmed | Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells |
title_short | Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells |
title_sort | monovalent engagement of the bcr activates ovalbumin-specific transnuclear b cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920557/ https://www.ncbi.nlm.nih.gov/pubmed/24493799 http://dx.doi.org/10.1084/jem.20131603 |
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