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Aberrant B Cell Signaling in Autoimmune Diseases

Aberrant B cell signaling plays a critical in role in various systemic and organ-specific autoimmune diseases. This is supported by genetic evidence by many functional studies in B cells from patients or specific animal models and by the observed efficacy of small-molecule inhibitors. In this review...

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Autores principales: Corneth, Odilia B. J., Neys, Stefan F. H., Hendriks, Rudi W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654300/
https://www.ncbi.nlm.nih.gov/pubmed/36359789
http://dx.doi.org/10.3390/cells11213391
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author Corneth, Odilia B. J.
Neys, Stefan F. H.
Hendriks, Rudi W.
author_facet Corneth, Odilia B. J.
Neys, Stefan F. H.
Hendriks, Rudi W.
author_sort Corneth, Odilia B. J.
collection PubMed
description Aberrant B cell signaling plays a critical in role in various systemic and organ-specific autoimmune diseases. This is supported by genetic evidence by many functional studies in B cells from patients or specific animal models and by the observed efficacy of small-molecule inhibitors. In this review, we first discuss key signal transduction pathways downstream of the B cell receptor (BCR) that ensure that autoreactive B cells are removed from the repertoire or functionally silenced. We provide an overview of aberrant BCR signaling that is associated with inappropriate B cell repertoire selection and activation or survival of peripheral B cell populations and plasma cells, finally leading to autoantibody formation. Next to BCR signaling, abnormalities in other signal transduction pathways have been implicated in autoimmune disease. These include reduced activity of several phosphates that are downstream of co-inhibitory receptors on B cells and increased levels of BAFF and APRIL, which support survival of B cells and plasma cells. Importantly, pathogenic synergy of the BCR and Toll-like receptors (TLR), which can be activated by endogenous ligands, such as self-nucleic acids, has been shown to enhance autoimmunity. Finally, we will briefly discuss therapeutic strategies for autoimmune disease based on interfering with signal transduction in B cells.
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spelling pubmed-96543002022-11-15 Aberrant B Cell Signaling in Autoimmune Diseases Corneth, Odilia B. J. Neys, Stefan F. H. Hendriks, Rudi W. Cells Review Aberrant B cell signaling plays a critical in role in various systemic and organ-specific autoimmune diseases. This is supported by genetic evidence by many functional studies in B cells from patients or specific animal models and by the observed efficacy of small-molecule inhibitors. In this review, we first discuss key signal transduction pathways downstream of the B cell receptor (BCR) that ensure that autoreactive B cells are removed from the repertoire or functionally silenced. We provide an overview of aberrant BCR signaling that is associated with inappropriate B cell repertoire selection and activation or survival of peripheral B cell populations and plasma cells, finally leading to autoantibody formation. Next to BCR signaling, abnormalities in other signal transduction pathways have been implicated in autoimmune disease. These include reduced activity of several phosphates that are downstream of co-inhibitory receptors on B cells and increased levels of BAFF and APRIL, which support survival of B cells and plasma cells. Importantly, pathogenic synergy of the BCR and Toll-like receptors (TLR), which can be activated by endogenous ligands, such as self-nucleic acids, has been shown to enhance autoimmunity. Finally, we will briefly discuss therapeutic strategies for autoimmune disease based on interfering with signal transduction in B cells. MDPI 2022-10-27 /pmc/articles/PMC9654300/ /pubmed/36359789 http://dx.doi.org/10.3390/cells11213391 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Corneth, Odilia B. J.
Neys, Stefan F. H.
Hendriks, Rudi W.
Aberrant B Cell Signaling in Autoimmune Diseases
title Aberrant B Cell Signaling in Autoimmune Diseases
title_full Aberrant B Cell Signaling in Autoimmune Diseases
title_fullStr Aberrant B Cell Signaling in Autoimmune Diseases
title_full_unstemmed Aberrant B Cell Signaling in Autoimmune Diseases
title_short Aberrant B Cell Signaling in Autoimmune Diseases
title_sort aberrant b cell signaling in autoimmune diseases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654300/
https://www.ncbi.nlm.nih.gov/pubmed/36359789
http://dx.doi.org/10.3390/cells11213391
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