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Variable immune response to SARS-CoV-2 mRNA vaccination in multiple sclerosis after rituximab treatment interruption
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.ORCID-id: 0000-0001-5384-8038
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).ORCID-id: 0000-0003-2018-8592
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Immunologi
Identifikatorer
URN: urn:nbn:se:umu:diva-199293OAI: oai:DiVA.org:umu-199293DiVA, id: diva2:1694936
Tillgänglig från: 2022-09-12 Skapad: 2022-09-12 Senast uppdaterad: 2023-07-03
Ingår i avhandling
1. Life and death of human B cells in health and disease
Öppna denna publikation i ny flik eller fönster >>Life and death of human B cells in health and disease
2022 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå Universitet, 2022. s. 84
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 2202
Nyckelord
b cells, antibody, hantavirus, germinal centre, phagocytosis, selection, DAF, vaccination, rituximab
Nationell ämneskategori
Immunologi
Identifikatorer
urn:nbn:se:umu:diva-199289 (URN)978-91-7855-883-4 (ISBN)978-91-7855-884-1 (ISBN)
Disputation
2022-10-07, 5B Stora hörsalen, Målpunkt P, Norrlands Universitetssjukhus, Umeå, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2022-09-16 Skapad: 2022-09-12 Senast uppdaterad: 2022-09-14Bibliografiskt granskad

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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.
Av organisationen
Institutionen för klinisk mikrobiologiInfektionssjukdomarInstitutionen för folkhälsa och klinisk medicinUmeå Centre for Microbial Research (UCMR)Institutionen för molekylärbiologi (Medicinska fakulteten)Molekylär Infektionsmedicin, Sverige (MIMS)Immunologi/immunkemiNeurovetenskaper
Immunologi

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