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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Main Authors: Justyna Polak, Johanna H. Wagnerberger, Silje Bøen Torsetnes, Ida Lindeman, Rune A. Aa. Høglund, Frode Vartdal, Ludvig M. Sollid, Andreas Lossius
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Cellular Neuroscience
Subjects:
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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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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