Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosis

Justyna Polak; Johanna H Wagnerberger; Silje Bøen Torsetnes; Ida Lindeman; Rune A Aa Høglund; Frode Vartdal; Ludvig M Sollid; Andreas Lossius

doi:10.3389/fncel.2023.1189709

Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosis

Front Cell Neurosci. 2023 Jun 8:17:1189709. doi: 10.3389/fncel.2023.1189709. eCollection 2023.

Authors

Justyna Polak^{1

2

3}, Johanna H Wagnerberger³, Silje Bøen Torsetnes⁴, Ida Lindeman^{1

2}, Rune A Aa Høglund^{4

5}, Frode Vartdal^{1

2}, Ludvig M Sollid^{1

2

5}, Andreas Lossius^{2

3

4}

Affiliations

¹ Department of Immunology, Oslo University Hospital, University of Oslo, Oslo, Norway.
² K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
³ Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
⁴ Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
⁵ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Abstract

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.

Keywords: B cells; IgG; cerebrospinal fluid; multiple sclerosis; oligoclonal bands (OCB); plasmablasts.

Grants and funding

This study was funded by grants from the Norwegian Women’s Public Health Association, the Norwegian Research Council (Project No. 314376), the South-Eastern Norway Regional Health Authority, the University of Oslo World-Leading Research Program on Human Immunology (WL-IMMUNOLOGY), and Stiftelsen K.G. Jebsen (Project No. SKGJ-MED-017). Additionally, JP and AL are the recipients of the Norwegian Neurological Association research prize in multiple sclerosis 2019 and 2020 provided by Sanofi Genzyme and Novartis. AL also received Odd Fellow’s Research Grant 2019.