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The chronically inflamed central nervous system provides niches for long-lived plasma cells
Although oligoclonal bands in the cerebrospinal fluid have been a hallmark of multiple sclerosis diagnosis for over three decades, the role of antibody-secreting cells in multiple sclerosis remains unclear. T and B cells are critical for multiple sclerosis pathogenesis, but increasing evidence sugge...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702095/ https://www.ncbi.nlm.nih.gov/pubmed/29178933 http://dx.doi.org/10.1186/s40478-017-0487-8 |
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author | Pollok, Karolin Mothes, Ronja Ulbricht, Carolin Liebheit, Alina Gerken, Jan David Uhlmann, Sylvia Paul, Friedemann Niesner, Raluca Radbruch, Helena Hauser, Anja Erika |
author_facet | Pollok, Karolin Mothes, Ronja Ulbricht, Carolin Liebheit, Alina Gerken, Jan David Uhlmann, Sylvia Paul, Friedemann Niesner, Raluca Radbruch, Helena Hauser, Anja Erika |
author_sort | Pollok, Karolin |
collection | PubMed |
description | Although oligoclonal bands in the cerebrospinal fluid have been a hallmark of multiple sclerosis diagnosis for over three decades, the role of antibody-secreting cells in multiple sclerosis remains unclear. T and B cells are critical for multiple sclerosis pathogenesis, but increasing evidence suggests that plasma cells also contribute, through secretion of autoantibodies. Long-lived plasma cells are known to drive various chronic inflammatory conditions as e.g. systemic lupus erythematosus, however, to what extent they are present in autoimmune central nervous system inflammation has not yet been investigated. In brain biopsies from multiple sclerosis patients and other neurological diseases, we could detect non-proliferating plasma cells (CD138(+)Ki67(−)) in the parenchyma. Based on this finding, we hypothesized that long-lived plasma cells can persist in the central nervous system (CNS). In order to test this hypothesis, we adapted the multiple sclerosis mouse model experimental autoimmune encephalomyelitis to generate a B cell memory response. Plasma cells were found in the meninges and the parenchyma of the inflamed spinal cord, surrounded by tissue areas resembling survival niches for these cells, characterized by an up-regulation of chemokines (CXCL12), adhesion molecules (VCAM-1) and survival factors (APRIL and BAFF). In order to determine the lifetime of plasma cells in the chronically inflamed CNS, we labeled the DNA of proliferating cells with 5-ethynyl-2′-deoxyuridine (EdU). Up to five weeks later, we could detect EdU(+) long-lived plasma cells in the murine CNS. To our knowledge, this is the first study describing non-proliferating plasma cells directly in the target tissue of a chronic inflammation in humans, as well as the first evidence demonstrating the ability of plasma cells to persist in the CNS, and the ability of the chronically inflamed CNS tissue to promote this persistence. Hence, our results suggest that the CNS provides survival niches for long-lived plasma cells, similar to the niches found in other organs. Targeting these cells in the CNS offers new perspectives for treatment of chronic autoimmune neuroinflammatory diseases, especially in patients who do not respond to conventional therapies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-017-0487-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5702095 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-57020952017-12-04 The chronically inflamed central nervous system provides niches for long-lived plasma cells Pollok, Karolin Mothes, Ronja Ulbricht, Carolin Liebheit, Alina Gerken, Jan David Uhlmann, Sylvia Paul, Friedemann Niesner, Raluca Radbruch, Helena Hauser, Anja Erika Acta Neuropathol Commun Research Although oligoclonal bands in the cerebrospinal fluid have been a hallmark of multiple sclerosis diagnosis for over three decades, the role of antibody-secreting cells in multiple sclerosis remains unclear. T and B cells are critical for multiple sclerosis pathogenesis, but increasing evidence suggests that plasma cells also contribute, through secretion of autoantibodies. Long-lived plasma cells are known to drive various chronic inflammatory conditions as e.g. systemic lupus erythematosus, however, to what extent they are present in autoimmune central nervous system inflammation has not yet been investigated. In brain biopsies from multiple sclerosis patients and other neurological diseases, we could detect non-proliferating plasma cells (CD138(+)Ki67(−)) in the parenchyma. Based on this finding, we hypothesized that long-lived plasma cells can persist in the central nervous system (CNS). In order to test this hypothesis, we adapted the multiple sclerosis mouse model experimental autoimmune encephalomyelitis to generate a B cell memory response. Plasma cells were found in the meninges and the parenchyma of the inflamed spinal cord, surrounded by tissue areas resembling survival niches for these cells, characterized by an up-regulation of chemokines (CXCL12), adhesion molecules (VCAM-1) and survival factors (APRIL and BAFF). In order to determine the lifetime of plasma cells in the chronically inflamed CNS, we labeled the DNA of proliferating cells with 5-ethynyl-2′-deoxyuridine (EdU). Up to five weeks later, we could detect EdU(+) long-lived plasma cells in the murine CNS. To our knowledge, this is the first study describing non-proliferating plasma cells directly in the target tissue of a chronic inflammation in humans, as well as the first evidence demonstrating the ability of plasma cells to persist in the CNS, and the ability of the chronically inflamed CNS tissue to promote this persistence. Hence, our results suggest that the CNS provides survival niches for long-lived plasma cells, similar to the niches found in other organs. Targeting these cells in the CNS offers new perspectives for treatment of chronic autoimmune neuroinflammatory diseases, especially in patients who do not respond to conventional therapies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-017-0487-8) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-25 /pmc/articles/PMC5702095/ /pubmed/29178933 http://dx.doi.org/10.1186/s40478-017-0487-8 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Pollok, Karolin Mothes, Ronja Ulbricht, Carolin Liebheit, Alina Gerken, Jan David Uhlmann, Sylvia Paul, Friedemann Niesner, Raluca Radbruch, Helena Hauser, Anja Erika The chronically inflamed central nervous system provides niches for long-lived plasma cells |
title | The chronically inflamed central nervous system provides niches for long-lived plasma cells |
title_full | The chronically inflamed central nervous system provides niches for long-lived plasma cells |
title_fullStr | The chronically inflamed central nervous system provides niches for long-lived plasma cells |
title_full_unstemmed | The chronically inflamed central nervous system provides niches for long-lived plasma cells |
title_short | The chronically inflamed central nervous system provides niches for long-lived plasma cells |
title_sort | chronically inflamed central nervous system provides niches for long-lived plasma cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702095/ https://www.ncbi.nlm.nih.gov/pubmed/29178933 http://dx.doi.org/10.1186/s40478-017-0487-8 |
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