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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.734282/full |
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| author | Niels J. M. Verstegen Niels J. M. Verstegen Victor Ubels Victor Ubels Hans V. Westerhoff Hans V. Westerhoff S. Marieke van Ham S. Marieke van Ham Matteo Barberis Matteo Barberis Matteo Barberis |
| author_facet | Niels J. M. Verstegen Niels J. M. Verstegen Victor Ubels Victor Ubels Hans V. Westerhoff Hans V. Westerhoff S. Marieke van Ham S. Marieke van Ham Matteo Barberis Matteo Barberis Matteo Barberis |
| author_sort | Niels J. M. Verstegen |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T19:19:43Z |
| format | Article |
| id | doaj.art-ec4019ff2f594d659270a9da72bde4d8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T19:19:43Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ec4019ff2f594d659270a9da72bde4d82022-12-21T21:35:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.734282734282System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell DifferentiationNiels J. M. Verstegen0Niels J. M. Verstegen1Victor Ubels2Victor Ubels3Hans V. Westerhoff4Hans V. Westerhoff5S. Marieke van Ham6S. Marieke van Ham7Matteo Barberis8Matteo Barberis9Matteo Barberis10Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsSynthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, NetherlandsSystems Biology, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United KingdomCentre for Mathematical and Computational Biology, CMCB, University of Surrey, Guildford, United KingdomSynthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, NetherlandsDepartment of Molecular Cell Physiology, VU University Amsterdam, Amsterdam, NetherlandsDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsSynthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, NetherlandsSynthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, NetherlandsSystems Biology, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United KingdomCentre for Mathematical and Computational Biology, CMCB, University of Surrey, Guildford, United KingdomGerminal 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.734282/fullsystems biologyT follicular helper cellsB cellsmathematical modelingB cell recycling and differentiationmemory B cell |
| spellingShingle | Niels J. M. Verstegen Niels J. M. Verstegen Victor Ubels Victor Ubels Hans V. Westerhoff Hans V. Westerhoff S. Marieke van Ham S. Marieke van Ham Matteo Barberis Matteo Barberis Matteo Barberis System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation Frontiers in Immunology systems biology T follicular helper cells B cells mathematical modeling B cell recycling and differentiation memory B cell |
| 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 | systems biology T follicular helper cells B cells mathematical modeling B cell recycling and differentiation memory B cell |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.734282/full |
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