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Thymic B Cells as a New Player in the Type 1 Diabetes Response

Type 1 diabetes (T1d) results from a sustained autoreactive T and B cell response towards insulin-producing β cells in the islets of Langerhans. The autoreactive nature of the condition has led to many investigations addressing the genetic or cellular changes in primary lymphoid tissues that impairs...

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Autores principales: Greaves, Richard B., Chen, Dawei, Green, E. Allison
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566354/
https://www.ncbi.nlm.nih.gov/pubmed/34745148
http://dx.doi.org/10.3389/fimmu.2021.772017
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author Greaves, Richard B.
Chen, Dawei
Green, E. Allison
author_facet Greaves, Richard B.
Chen, Dawei
Green, E. Allison
author_sort Greaves, Richard B.
collection PubMed
description Type 1 diabetes (T1d) results from a sustained autoreactive T and B cell response towards insulin-producing β cells in the islets of Langerhans. The autoreactive nature of the condition has led to many investigations addressing the genetic or cellular changes in primary lymphoid tissues that impairs central tolerance- a key process in the deletion of autoreactive T and B cells during their development. For T cells, these studies have largely focused on medullary thymic epithelial cells (mTECs) critical for the effective negative selection of autoreactive T cells in the thymus. Recently, a new cellular player that impacts positively or negatively on the deletion of autoreactive T cells during their development has come to light, thymic B cells. Normally a small population within the thymus of mouse and man, thymic B cells expand in T1d as well as other autoimmune conditions, reside in thymic ectopic germinal centres and secrete autoantibodies that bind selective mTECs precipitating mTEC death. In this review we will discuss the ontogeny, characteristics and functionality of thymic B cells in healthy and autoimmune settings. Furthermore, we explore how in silico approaches may help decipher the complex cellular interplay of thymic B cells with other cells within the thymic microenvironment leading to new avenues for therapeutic intervention.
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spelling pubmed-85663542021-11-05 Thymic B Cells as a New Player in the Type 1 Diabetes Response Greaves, Richard B. Chen, Dawei Green, E. Allison Front Immunol Immunology Type 1 diabetes (T1d) results from a sustained autoreactive T and B cell response towards insulin-producing β cells in the islets of Langerhans. The autoreactive nature of the condition has led to many investigations addressing the genetic or cellular changes in primary lymphoid tissues that impairs central tolerance- a key process in the deletion of autoreactive T and B cells during their development. For T cells, these studies have largely focused on medullary thymic epithelial cells (mTECs) critical for the effective negative selection of autoreactive T cells in the thymus. Recently, a new cellular player that impacts positively or negatively on the deletion of autoreactive T cells during their development has come to light, thymic B cells. Normally a small population within the thymus of mouse and man, thymic B cells expand in T1d as well as other autoimmune conditions, reside in thymic ectopic germinal centres and secrete autoantibodies that bind selective mTECs precipitating mTEC death. In this review we will discuss the ontogeny, characteristics and functionality of thymic B cells in healthy and autoimmune settings. Furthermore, we explore how in silico approaches may help decipher the complex cellular interplay of thymic B cells with other cells within the thymic microenvironment leading to new avenues for therapeutic intervention. Frontiers Media S.A. 2021-10-21 /pmc/articles/PMC8566354/ /pubmed/34745148 http://dx.doi.org/10.3389/fimmu.2021.772017 Text en Copyright © 2021 Greaves, Chen and Green 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
Greaves, Richard B.
Chen, Dawei
Green, E. Allison
Thymic B Cells as a New Player in the Type 1 Diabetes Response
title Thymic B Cells as a New Player in the Type 1 Diabetes Response
title_full Thymic B Cells as a New Player in the Type 1 Diabetes Response
title_fullStr Thymic B Cells as a New Player in the Type 1 Diabetes Response
title_full_unstemmed Thymic B Cells as a New Player in the Type 1 Diabetes Response
title_short Thymic B Cells as a New Player in the Type 1 Diabetes Response
title_sort thymic b cells as a new player in the type 1 diabetes response
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566354/
https://www.ncbi.nlm.nih.gov/pubmed/34745148
http://dx.doi.org/10.3389/fimmu.2021.772017
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