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Variable immune response to SARS-CoV-2 mRNA vaccination in multiple sclerosis after rituximab treatment interruption
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.ORCID iD: 0000-0001-5384-8038
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).ORCID iD: 0000-0003-2018-8592
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(English)Manuscript (preprint) (Other academic)
National Category
Immunology
Identifiers
URN: urn:nbn:se:umu:diva-199293OAI: oai:DiVA.org:umu-199293DiVA, id: diva2:1694936
Available from: 2022-09-12 Created: 2022-09-12 Last updated: 2023-07-03
In thesis
1. Life and death of human B cells in health and disease
Open this publication in new window or tab >>Life and death of human B cells in health and disease
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

B cells provide one of the key mechanisms of immunological memory, which is theproduction of neutralising antibodies. How B cells respond to infections and vaccinationgives clues to how the development of the immunological memory is facilitated, and canthus lead to a deeper understanding of why the immune system sometimesmalfunctions. This thesis focuses on the human B cell responses in three differentsettings: Acute viral infection, mechanisms involved in germinal centre responses, andvaccination upon interrupted B cell depletion therapy in patients with multiple sclerosis(MS). We have found that during acute Puumala-orthohantavirus (PUUV) infection, Bcells activate on a large scale and derive a phenotype similar to previous observations inautoimmune diseases and chronic infections. Patients with PUUV infection also haddecreased expression of the complement regulatory protein Decay-Accelerating Factor(DAF) at an early stage in the disease. Here, we hypothesised that this might be a resultof a robust B cell response, and therefore we continued to assess B cells at the peripheralsites of their maturation. We found that B cells downregulated the complementinhibitory protein during the germinal centre reaction, which also primed the cells forphagocytosis. This finding shed light to the mechanisms that control B cell homeostasis.Finally, we assessed the B cell responses towards vaccination in patients with MS afterinterruption of their B cell depletion therapy. Here we showed that the patients yieldedexpansion of vaccination-specific memory B cells. However, these memory B cells didnot comprise expansion of DAFlo cells, in contrast to the non-MS control individuals.We speculated that the B cell depletion might have an impact on the formation of B cellmemory after interrupted treatment. Taken together, this thesis contributes to theoverall understanding of the life cycle of B cells, in the context of infection, vaccination,and homeostasis.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2022. p. 84
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2202
Keywords
b cells, antibody, hantavirus, germinal centre, phagocytosis, selection, DAF, vaccination, rituximab
National Category
Immunology
Identifiers
urn:nbn:se:umu:diva-199289 (URN)978-91-7855-883-4 (ISBN)978-91-7855-884-1 (ISBN)
Public defence
2022-10-07, 5B Stora hörsalen, Målpunkt P, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2022-09-16 Created: 2022-09-12 Last updated: 2022-09-14Bibliographically approved

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Gröning, RemigiusDernstedt, AndyGardfjäll, JennyAhlm, ClasNormark, JohanSundström, PeterForsell, Mattias N. E.

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Gröning, RemigiusDernstedt, AndyGardfjäll, JennyAhlm, ClasNormark, JohanSundström, PeterForsell, Mattias N. E.
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Department of Clinical MicrobiologyInfectious DiseasesDepartment of Public Health and Clinical MedicineUmeå Centre for Microbial Research (UCMR)Department of Molecular Biology (Faculty of Medicine)Molecular Infection Medicine Sweden (MIMS)Immunology/ImmunchemistryNeurosciences
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CiteExportLink to record
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