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Thymic B Cells Promote Germinal Center-Like Structures and the Expansion of Follicular Helper T Cells in Lupus-Prone Mice

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of autoreactive T and B cells, autoantibody production, and immune complex deposition in various organs. Previous evidence showed abnormal accumulation of B cells in the thymus of lupus-prone mice, but the ro...

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Autores principales: Hidalgo, Yessia, Núñez, Sarah, Fuenzalida, Maria Jose, Flores-Santibáñez, Felipe, Sáez, Pablo J., Dorner, Jessica, Lennon-Dumenil, Ana-Maria, Martínez, Victor, Zorn, Emmanuel, Rosemblatt, Mario, Sauma, Daniela, Bono, Maria Rosa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199236/
https://www.ncbi.nlm.nih.gov/pubmed/32411134
http://dx.doi.org/10.3389/fimmu.2020.00696
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author Hidalgo, Yessia
Núñez, Sarah
Fuenzalida, Maria Jose
Flores-Santibáñez, Felipe
Sáez, Pablo J.
Dorner, Jessica
Lennon-Dumenil, Ana-Maria
Martínez, Victor
Zorn, Emmanuel
Rosemblatt, Mario
Sauma, Daniela
Bono, Maria Rosa
author_facet Hidalgo, Yessia
Núñez, Sarah
Fuenzalida, Maria Jose
Flores-Santibáñez, Felipe
Sáez, Pablo J.
Dorner, Jessica
Lennon-Dumenil, Ana-Maria
Martínez, Victor
Zorn, Emmanuel
Rosemblatt, Mario
Sauma, Daniela
Bono, Maria Rosa
author_sort Hidalgo, Yessia
collection PubMed
description Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of autoreactive T and B cells, autoantibody production, and immune complex deposition in various organs. Previous evidence showed abnormal accumulation of B cells in the thymus of lupus-prone mice, but the role of this population in the progression of the disease remains mostly undefined. Here we analyzed the spatial distribution, function, and properties of this thymic B cell population in the BWF1 murine model of SLE. We found that in diseased animals, thymic B cells proliferate, and cluster in structures that resemble ectopic germinal centers. Moreover, we detected antibody-secreting cells in the thymus of diseased-BWF1 mice that produce anti-dsDNA IgG autoantibodies. We also found that thymic B cells from diseased-BWF1 mice induced the differentiation of thymocytes to follicular helper T cells (T(FH)). These data suggest that the accumulation of B cells in the thymus of BWF1 mice results in the formation of germinal center-like structures and the expansion of a T(FH) population, which may, in turn, activate and differentiate B cells into autoreactive plasma cells. Therefore, the thymus emerges as an important niche that supports the maintenance of the pathogenic humoral response in the development of murine SLE.
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spelling pubmed-71992362020-05-14 Thymic B Cells Promote Germinal Center-Like Structures and the Expansion of Follicular Helper T Cells in Lupus-Prone Mice Hidalgo, Yessia Núñez, Sarah Fuenzalida, Maria Jose Flores-Santibáñez, Felipe Sáez, Pablo J. Dorner, Jessica Lennon-Dumenil, Ana-Maria Martínez, Victor Zorn, Emmanuel Rosemblatt, Mario Sauma, Daniela Bono, Maria Rosa Front Immunol Immunology Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of autoreactive T and B cells, autoantibody production, and immune complex deposition in various organs. Previous evidence showed abnormal accumulation of B cells in the thymus of lupus-prone mice, but the role of this population in the progression of the disease remains mostly undefined. Here we analyzed the spatial distribution, function, and properties of this thymic B cell population in the BWF1 murine model of SLE. We found that in diseased animals, thymic B cells proliferate, and cluster in structures that resemble ectopic germinal centers. Moreover, we detected antibody-secreting cells in the thymus of diseased-BWF1 mice that produce anti-dsDNA IgG autoantibodies. We also found that thymic B cells from diseased-BWF1 mice induced the differentiation of thymocytes to follicular helper T cells (T(FH)). These data suggest that the accumulation of B cells in the thymus of BWF1 mice results in the formation of germinal center-like structures and the expansion of a T(FH) population, which may, in turn, activate and differentiate B cells into autoreactive plasma cells. Therefore, the thymus emerges as an important niche that supports the maintenance of the pathogenic humoral response in the development of murine SLE. Frontiers Media S.A. 2020-04-28 /pmc/articles/PMC7199236/ /pubmed/32411134 http://dx.doi.org/10.3389/fimmu.2020.00696 Text en Copyright © 2020 Hidalgo, Núñez, Fuenzalida, Flores-Santibáñez, Sáez, Dorner, Lennon-Dumenil, Martínez, Zorn, Rosemblatt, Sauma and Bono. http://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
Hidalgo, Yessia
Núñez, Sarah
Fuenzalida, Maria Jose
Flores-Santibáñez, Felipe
Sáez, Pablo J.
Dorner, Jessica
Lennon-Dumenil, Ana-Maria
Martínez, Victor
Zorn, Emmanuel
Rosemblatt, Mario
Sauma, Daniela
Bono, Maria Rosa
Thymic B Cells Promote Germinal Center-Like Structures and the Expansion of Follicular Helper T Cells in Lupus-Prone Mice
title Thymic B Cells Promote Germinal Center-Like Structures and the Expansion of Follicular Helper T Cells in Lupus-Prone Mice
title_full Thymic B Cells Promote Germinal Center-Like Structures and the Expansion of Follicular Helper T Cells in Lupus-Prone Mice
title_fullStr Thymic B Cells Promote Germinal Center-Like Structures and the Expansion of Follicular Helper T Cells in Lupus-Prone Mice
title_full_unstemmed Thymic B Cells Promote Germinal Center-Like Structures and the Expansion of Follicular Helper T Cells in Lupus-Prone Mice
title_short Thymic B Cells Promote Germinal Center-Like Structures and the Expansion of Follicular Helper T Cells in Lupus-Prone Mice
title_sort thymic b cells promote germinal center-like structures and the expansion of follicular helper t cells in lupus-prone mice
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199236/
https://www.ncbi.nlm.nih.gov/pubmed/32411134
http://dx.doi.org/10.3389/fimmu.2020.00696
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