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B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease
BACKGROUND AND OBJECTIVES: To assess the molecular landscape of B-cell subpopulations across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We performed B-cell transcriptomic profiles via single-cell RNA sequencing across CSF, blood, and bone marrow...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409132/ https://www.ncbi.nlm.nih.gov/pubmed/34465614 http://dx.doi.org/10.1212/NXI.0000000000001070 |
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author | Zhang, Chao Zhang, Tian-Xiang Liu, Ye Jia, Dongmei Zeng, Pei Du, Chen Yuan, Meng Liu, Qiang Wang, Yongjun Shi, Fu-Dong |
author_facet | Zhang, Chao Zhang, Tian-Xiang Liu, Ye Jia, Dongmei Zeng, Pei Du, Chen Yuan, Meng Liu, Qiang Wang, Yongjun Shi, Fu-Dong |
author_sort | Zhang, Chao |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: To assess the molecular landscape of B-cell subpopulations across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We performed B-cell transcriptomic profiles via single-cell RNA sequencing across CSF, blood, and bone marrow in patients with NMOSD. RESULTS: Across the tissue types tested, 4 major subpopulations of B cells with distinct signatures were identified: naive B cells, memory B cells, age-associated B cells, and antibody-secreting cells (ASCs). NMOSD B cells show proinflammatory activity and increased expression of chemokine receptor genes (CXCR3 and CXCR4). Circulating B cells display an increase of antigen presentation markers (CD40 and CD83), as well as activation signatures (FOS, CD69, and JUN). In contrast, the bone marrow B-cell population contains a large ASC fraction with increased oxidative and metabolic activity reflected by COX genes and ATP synthase genes. Typically, NMOSD B cells become hyperresponsive to type I interferon, which facilitates B-cell maturation and anti–aquaporin-4 autoantibody production. The pool of ASCs in blood and CSF were significantly elevated in NMOSD. Both CD19(−) and CD19(+) ASCs could be ablated by tocilizumab, but not rituximab treatment in NMOSD. DISCUSSION: B cells are compartmentally fine tuned toward autoreactivity in NMOSD and become hyperreactive to type I interferon. Inhibition of type I interferon pathway may provide a new therapeutic avenue for NMOSD. |
format | Online Article Text |
id | pubmed-8409132 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-84091322021-09-01 B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease Zhang, Chao Zhang, Tian-Xiang Liu, Ye Jia, Dongmei Zeng, Pei Du, Chen Yuan, Meng Liu, Qiang Wang, Yongjun Shi, Fu-Dong Neurol Neuroimmunol Neuroinflamm Article BACKGROUND AND OBJECTIVES: To assess the molecular landscape of B-cell subpopulations across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We performed B-cell transcriptomic profiles via single-cell RNA sequencing across CSF, blood, and bone marrow in patients with NMOSD. RESULTS: Across the tissue types tested, 4 major subpopulations of B cells with distinct signatures were identified: naive B cells, memory B cells, age-associated B cells, and antibody-secreting cells (ASCs). NMOSD B cells show proinflammatory activity and increased expression of chemokine receptor genes (CXCR3 and CXCR4). Circulating B cells display an increase of antigen presentation markers (CD40 and CD83), as well as activation signatures (FOS, CD69, and JUN). In contrast, the bone marrow B-cell population contains a large ASC fraction with increased oxidative and metabolic activity reflected by COX genes and ATP synthase genes. Typically, NMOSD B cells become hyperresponsive to type I interferon, which facilitates B-cell maturation and anti–aquaporin-4 autoantibody production. The pool of ASCs in blood and CSF were significantly elevated in NMOSD. Both CD19(−) and CD19(+) ASCs could be ablated by tocilizumab, but not rituximab treatment in NMOSD. DISCUSSION: B cells are compartmentally fine tuned toward autoreactivity in NMOSD and become hyperreactive to type I interferon. Inhibition of type I interferon pathway may provide a new therapeutic avenue for NMOSD. Lippincott Williams & Wilkins 2021-08-31 /pmc/articles/PMC8409132/ /pubmed/34465614 http://dx.doi.org/10.1212/NXI.0000000000001070 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Article Zhang, Chao Zhang, Tian-Xiang Liu, Ye Jia, Dongmei Zeng, Pei Du, Chen Yuan, Meng Liu, Qiang Wang, Yongjun Shi, Fu-Dong B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease |
title | B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease |
title_full | B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease |
title_fullStr | B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease |
title_full_unstemmed | B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease |
title_short | B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease |
title_sort | b-cell compartmental features and molecular basis for therapy in autoimmune disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409132/ https://www.ncbi.nlm.nih.gov/pubmed/34465614 http://dx.doi.org/10.1212/NXI.0000000000001070 |
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