The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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Digital Trial Lecture – time and place
Adjudication committee
- First opponent: Professor Sai Reddy, ETH Zürich (Swiss Federal Institute of Technology in Zurich), Switzerland
- Second opponent: Professor Anja Hauser, German Rheumatism Research Centre Berlin (DRFZ), Germany
- Third member and chair of the evaluation committee: Professor Marit Inngjerdingen, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor Frode Lars Jahnsen, Faculty of Medicine, University of Oslo
Principal Supervisor
Professor Ludvig Magne Sollid, Faculty of Medicine, University of Oslo
Summary
Cells of the B-lineage are needed for a healthy immune system, but may also be involved in a range of diseases including autoimmune diseases such as coeliac disease and multiple sclerosis. Exactly how B-lineage cells contribute to coeliac disease and multiple sclerosis is largely unknown.
In this thesis, we contributed to the existing toolbox of computational methods by developing BraCeR. BraCeR enables reconstruction of B-cell receptor (BCR) sequences from single-cell RNA-sequencing data, and infers clonally related cells. We next used single-cell RNA-sequencing and applied BraCeR to study B-lineage cells in coeliac disease and multiple sclerosis.
Our integrated approach revealed new insights into the link between aspects of B-cell responses such as clonality, antigen specificity, isotype, somatic hypermutation, cell longevity, and transcriptional phenotype at a single-cell resolution. We showed that disease-specific plasma cells in the coeliac lesion are skewed towards a short-lived phenotype, and differ transcriptionally from plasma cells of other, unknown specificities. Further, we identified novel BCR repertoire characteristics in both diseases. For the first time, we revealed that the BCR repertoire is skewed in antibody-secreting cells of the IgG1 isotype subclass in multiple sclerosis patients depending on allelic polymorphisms in the IGHG1 gene.
The work presented in this thesis revealed new insights into B-lineage cells in autoimmunity and health, and provided a novel computational tool that may be used by others for the study of B-lineage cells in various settings.
Additional information
Contact the research support staff.