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System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation

Germinal center (GC) reactions are vital to the correct functioning of the adaptive immune system, through formation of high affinity, class switched antibodies. GCs are transient anatomical structures in secondary lymphoid organs where specific B cells, after recognition of antigen and with T cell...

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Autores principales: Verstegen, Niels J. M., Ubels, Victor, Westerhoff, Hans V., van Ham, S. Marieke, Barberis, Matteo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488341/
https://www.ncbi.nlm.nih.gov/pubmed/34616402
http://dx.doi.org/10.3389/fimmu.2021.734282
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author Verstegen, Niels J. M.
Ubels, Victor
Westerhoff, Hans V.
van Ham, S. Marieke
Barberis, Matteo
author_facet Verstegen, Niels J. M.
Ubels, Victor
Westerhoff, Hans V.
van Ham, S. Marieke
Barberis, Matteo
author_sort Verstegen, Niels J. M.
collection PubMed
description Germinal center (GC) reactions are vital to the correct functioning of the adaptive immune system, through formation of high affinity, class switched antibodies. GCs are transient anatomical structures in secondary lymphoid organs where specific B cells, after recognition of antigen and with T cell help, undergo class switching. Subsequently, B cells cycle between zones of proliferation and somatic hypermutation and zones where renewed antigen acquisition and T cell help allows for selection of high affinity B cells (affinity maturation). Eventually GC B cells first differentiate into long-lived memory B cells (MBC) and finally into plasma cells (PC) that partially migrate to the bone marrow to encapsulate into long-lived survival niches. The regulation of GC reactions is a highly dynamically coordinated process that occurs between various cells and molecules that change in their signals. Here, we present a system-level perspective of T cell-mediated GC B cell differentiation, presenting and discussing the experimental and computational efforts on the regulation of the GCs. We aim to integrate Systems Biology with B cell biology, to advance elucidation of the regulation of high-affinity, class switched antibody formation, thus to shed light on the delicate functioning of the adaptive immune system. Specifically, we: i) review experimental findings of internal and external factors driving various GC dynamics, such as GC initiation, maturation and GCBC fate determination; ii) draw comparisons between experimental observations and mathematical modeling investigations; and iii) discuss and reflect on current strategies of modeling efforts, to elucidate B cell behavior during the GC tract. Finally, perspectives are specifically given on to the areas where a Systems Biology approach may be useful to predict novel GCBC-T cell interaction dynamics.
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spelling pubmed-84883412021-10-05 System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation Verstegen, Niels J. M. Ubels, Victor Westerhoff, Hans V. van Ham, S. Marieke Barberis, Matteo Front Immunol Immunology Germinal center (GC) reactions are vital to the correct functioning of the adaptive immune system, through formation of high affinity, class switched antibodies. GCs are transient anatomical structures in secondary lymphoid organs where specific B cells, after recognition of antigen and with T cell help, undergo class switching. Subsequently, B cells cycle between zones of proliferation and somatic hypermutation and zones where renewed antigen acquisition and T cell help allows for selection of high affinity B cells (affinity maturation). Eventually GC B cells first differentiate into long-lived memory B cells (MBC) and finally into plasma cells (PC) that partially migrate to the bone marrow to encapsulate into long-lived survival niches. The regulation of GC reactions is a highly dynamically coordinated process that occurs between various cells and molecules that change in their signals. Here, we present a system-level perspective of T cell-mediated GC B cell differentiation, presenting and discussing the experimental and computational efforts on the regulation of the GCs. We aim to integrate Systems Biology with B cell biology, to advance elucidation of the regulation of high-affinity, class switched antibody formation, thus to shed light on the delicate functioning of the adaptive immune system. Specifically, we: i) review experimental findings of internal and external factors driving various GC dynamics, such as GC initiation, maturation and GCBC fate determination; ii) draw comparisons between experimental observations and mathematical modeling investigations; and iii) discuss and reflect on current strategies of modeling efforts, to elucidate B cell behavior during the GC tract. Finally, perspectives are specifically given on to the areas where a Systems Biology approach may be useful to predict novel GCBC-T cell interaction dynamics. Frontiers Media S.A. 2021-09-20 /pmc/articles/PMC8488341/ /pubmed/34616402 http://dx.doi.org/10.3389/fimmu.2021.734282 Text en Copyright © 2021 Verstegen, Ubels, Westerhoff, van Ham and Barberis https://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 Immunology
Verstegen, Niels J. M.
Ubels, Victor
Westerhoff, Hans V.
van Ham, S. Marieke
Barberis, Matteo
System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation
title System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation
title_full System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation
title_fullStr System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation
title_full_unstemmed System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation
title_short System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation
title_sort system-level scenarios for the elucidation of t cell-mediated germinal center b cell differentiation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488341/
https://www.ncbi.nlm.nih.gov/pubmed/34616402
http://dx.doi.org/10.3389/fimmu.2021.734282
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