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Tingible body macrophages arise from lymph node–resident precursors and uptake B cells by dendrites

Antibody affinity maturation depends on the formation of germinal centers (GCs) in lymph nodes. This process generates a massive number of apoptotic B cells, which are removed by a specialized subset of phagocytes, known as tingible body macrophages (TBMs). Although defects in these cells are associ...

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Autores principales: Gurwicz, Neta, Stoler-Barak, Liat, Schwan, Niklas, Bandyopadhyay, Arnab, Meyer-Hermann, Michael, Shulman, Ziv
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900388/
https://www.ncbi.nlm.nih.gov/pubmed/36705667
http://dx.doi.org/10.1084/jem.20222173
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author Gurwicz, Neta
Stoler-Barak, Liat
Schwan, Niklas
Bandyopadhyay, Arnab
Meyer-Hermann, Michael
Shulman, Ziv
author_facet Gurwicz, Neta
Stoler-Barak, Liat
Schwan, Niklas
Bandyopadhyay, Arnab
Meyer-Hermann, Michael
Shulman, Ziv
author_sort Gurwicz, Neta
collection PubMed
description Antibody affinity maturation depends on the formation of germinal centers (GCs) in lymph nodes. This process generates a massive number of apoptotic B cells, which are removed by a specialized subset of phagocytes, known as tingible body macrophages (TBMs). Although defects in these cells are associated with pathological conditions, the identity of their precursors and the dynamics of dying GC B cell disposal remained unknown. Here, we demonstrate that TBMs originate from pre-existing lymph node–resident precursors that enter the lymph node follicles in a GC-dependent manner. Intravital imaging shows that TBMs are stationary cells that selectively phagocytose GC B cells via highly dynamic protrusions and accommodate the final stages of B cell apoptosis. Cell-specific depletion and chimeric mouse models revealed that GC B cells drive TBM formation from bone marrow–derived precursors stationed within lymphoid organs prior to the immune challenge. Understanding TBM dynamics and function may explain the emergence of various antibody-mediated autoimmune conditions.
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spelling pubmed-99003882023-07-27 Tingible body macrophages arise from lymph node–resident precursors and uptake B cells by dendrites Gurwicz, Neta Stoler-Barak, Liat Schwan, Niklas Bandyopadhyay, Arnab Meyer-Hermann, Michael Shulman, Ziv J Exp Med Article Antibody affinity maturation depends on the formation of germinal centers (GCs) in lymph nodes. This process generates a massive number of apoptotic B cells, which are removed by a specialized subset of phagocytes, known as tingible body macrophages (TBMs). Although defects in these cells are associated with pathological conditions, the identity of their precursors and the dynamics of dying GC B cell disposal remained unknown. Here, we demonstrate that TBMs originate from pre-existing lymph node–resident precursors that enter the lymph node follicles in a GC-dependent manner. Intravital imaging shows that TBMs are stationary cells that selectively phagocytose GC B cells via highly dynamic protrusions and accommodate the final stages of B cell apoptosis. Cell-specific depletion and chimeric mouse models revealed that GC B cells drive TBM formation from bone marrow–derived precursors stationed within lymphoid organs prior to the immune challenge. Understanding TBM dynamics and function may explain the emergence of various antibody-mediated autoimmune conditions. Rockefeller University Press 2023-01-27 /pmc/articles/PMC9900388/ /pubmed/36705667 http://dx.doi.org/10.1084/jem.20222173 Text en © 2023 Gurwicz et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/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 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Gurwicz, Neta
Stoler-Barak, Liat
Schwan, Niklas
Bandyopadhyay, Arnab
Meyer-Hermann, Michael
Shulman, Ziv
Tingible body macrophages arise from lymph node–resident precursors and uptake B cells by dendrites
title Tingible body macrophages arise from lymph node–resident precursors and uptake B cells by dendrites
title_full Tingible body macrophages arise from lymph node–resident precursors and uptake B cells by dendrites
title_fullStr Tingible body macrophages arise from lymph node–resident precursors and uptake B cells by dendrites
title_full_unstemmed Tingible body macrophages arise from lymph node–resident precursors and uptake B cells by dendrites
title_short Tingible body macrophages arise from lymph node–resident precursors and uptake B cells by dendrites
title_sort tingible body macrophages arise from lymph node–resident precursors and uptake b cells by dendrites
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900388/
https://www.ncbi.nlm.nih.gov/pubmed/36705667
http://dx.doi.org/10.1084/jem.20222173
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