Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosis
The phenotypes of B lineage cells that produce oligoclonal IgG in multiple sclerosis have not been unequivocally determined. Here, we utilized single-cell RNA-seq data of intrathecal B lineage cells in combination with mass spectrometry of intrathecally synthesized IgG to identify its cellular sourc...
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Frontiers Media S.A.
2023-06-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1189709/full |
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author | Justyna Polak Justyna Polak Justyna Polak Johanna H. Wagnerberger Silje Bøen Torsetnes Ida Lindeman Ida Lindeman Rune A. Aa. Høglund Rune A. Aa. Høglund Frode Vartdal Frode Vartdal Ludvig M. Sollid Ludvig M. Sollid Ludvig M. Sollid Andreas Lossius Andreas Lossius Andreas Lossius |
author_facet | Justyna Polak Justyna Polak Justyna Polak Johanna H. Wagnerberger Silje Bøen Torsetnes Ida Lindeman Ida Lindeman Rune A. Aa. Høglund Rune A. Aa. Høglund Frode Vartdal Frode Vartdal Ludvig M. Sollid Ludvig M. Sollid Ludvig M. Sollid Andreas Lossius Andreas Lossius Andreas Lossius |
author_sort | Justyna Polak |
collection | DOAJ |
description | The phenotypes of B lineage cells that produce oligoclonal IgG in multiple sclerosis have not been unequivocally determined. Here, we utilized single-cell RNA-seq data of intrathecal B lineage cells in combination with mass spectrometry of intrathecally synthesized IgG to identify its cellular source. We found that the intrathecally produced IgG matched a larger fraction of clonally expanded antibody-secreting cells compared to singletons. The IgG was traced back to two clonally related clusters of antibody-secreting cells, one comprising highly proliferating cells, and the other consisting of more differentiated cells expressing genes associated with immunoglobulin synthesis. These findings suggest some degree of heterogeneity among cells that produce oligoclonal IgG in multiple sclerosis. |
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id | doaj.art-a63c77d89e504ac99db7f777b9903251 |
institution | Directory Open Access Journal |
issn | 1662-5102 |
language | English |
last_indexed | 2024-03-13T06:47:36Z |
publishDate | 2023-06-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Cellular Neuroscience |
spelling | doaj.art-a63c77d89e504ac99db7f777b99032512023-06-08T05:11:11ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-06-011710.3389/fncel.2023.11897091189709Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosisJustyna Polak0Justyna Polak1Justyna Polak2Johanna H. Wagnerberger3Silje Bøen Torsetnes4Ida Lindeman5Ida Lindeman6Rune A. Aa. Høglund7Rune A. Aa. Høglund8Frode Vartdal9Frode Vartdal10Ludvig M. Sollid11Ludvig M. Sollid12Ludvig M. Sollid13Andreas Lossius14Andreas Lossius15Andreas Lossius16Department of Immunology, Oslo University Hospital, University of Oslo, Oslo, NorwayK.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, NorwayDepartment of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, NorwayDepartment of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, NorwayDepartment of Neurology, Akershus University Hospital, Lørenskog, NorwayDepartment of Immunology, Oslo University Hospital, University of Oslo, Oslo, NorwayK.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, NorwayDepartment of Neurology, Akershus University Hospital, Lørenskog, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Immunology, Oslo University Hospital, University of Oslo, Oslo, NorwayK.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, NorwayDepartment of Immunology, Oslo University Hospital, University of Oslo, Oslo, NorwayK.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayK.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, NorwayDepartment of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, NorwayDepartment of Neurology, Akershus University Hospital, Lørenskog, NorwayThe phenotypes of B lineage cells that produce oligoclonal IgG in multiple sclerosis have not been unequivocally determined. Here, we utilized single-cell RNA-seq data of intrathecal B lineage cells in combination with mass spectrometry of intrathecally synthesized IgG to identify its cellular source. We found that the intrathecally produced IgG matched a larger fraction of clonally expanded antibody-secreting cells compared to singletons. The IgG was traced back to two clonally related clusters of antibody-secreting cells, one comprising highly proliferating cells, and the other consisting of more differentiated cells expressing genes associated with immunoglobulin synthesis. These findings suggest some degree of heterogeneity among cells that produce oligoclonal IgG in multiple sclerosis.https://www.frontiersin.org/articles/10.3389/fncel.2023.1189709/fullmultiple sclerosisB cellsplasmablastsoligoclonal bands (OCB)IgGcerebrospinal fluid |
spellingShingle | Justyna Polak Justyna Polak Justyna Polak Johanna H. Wagnerberger Silje Bøen Torsetnes Ida Lindeman Ida Lindeman Rune A. Aa. Høglund Rune A. Aa. Høglund Frode Vartdal Frode Vartdal Ludvig M. Sollid Ludvig M. Sollid Ludvig M. Sollid Andreas Lossius Andreas Lossius Andreas Lossius Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosis Frontiers in Cellular Neuroscience multiple sclerosis B cells plasmablasts oligoclonal bands (OCB) IgG cerebrospinal fluid |
title | Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosis |
title_full | Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosis |
title_fullStr | Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosis |
title_full_unstemmed | Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosis |
title_short | Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosis |
title_sort | single cell transcriptomics combined with proteomics of intrathecal igg reveal transcriptional heterogeneity of oligoclonal igg secreting cells in multiple sclerosis |
topic | multiple sclerosis B cells plasmablasts oligoclonal bands (OCB) IgG cerebrospinal fluid |
url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1189709/full |
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