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Myelin protein zero...
Myelin protein zero is naturally processed in IgM MGUS B cells : Aberrant triggering of patient T cells
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- Hellqvist, Eva, 1978- (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Kvarnström, Maria (författare)
- Linköpings universitet,Klinisk immunologi,Hälsouniversitetet
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- Söderberg, Anita (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Wrethem, Magnus (författare)
- Linköpings universitet,Neurologi,Hälsouniversitetet
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- Ernerudh, Jan (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Klinisk immunologi,Hälsouniversitetet,Klinisk immunologi och transfusionsmedicin
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- Rosén, Anders (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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(creator_code:org_t)
- 2009-12-16
- 2010
- Engelska.
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 95:4, s. 627-636
- Relaterad länk:
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https://doi.org/10.3...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Background and Objectives: Monoclonal gammopathy of undetermined significance (MGUS) of IgM isotype is a condition with clonally expanded B cells, recently suggested having an infectious origin. MGUS is frequently associated with polyneuropathy and antibodies against myelin protein zero (P0), whereas the role of the T cells remains largely unknown. Here we have analyzed P0-specific B cells, as antigen-presenting cells, and their capacity to activate T helper cells. Design and Methods: We used a well-characterized MGUS-derived B cell line, TJ2, expressing anti-P0 IgM. The ability of TJ2 cells to bind, endocytose, process, and present P0 was investigated by receptor-clustering and immunofluorescence. The activation of P0-specific autologous T cells was studied by measuring IL2 and IFNγ with flow cytometry, immunobeads, and ELISPOT. Results: Surface-receptor clustering and endocytosis of receptor-ligand (IgM/P0) complexes were pronounced after P0 exposure. Naturally processed or synthetic P0 peptide (194-208)-pulsed TJ2 cells significantly induced IL2 secretion from autologous T cells compared to control antigen pulsed cells (p<0 .001). The numbers of IFNγ producing T helper cells, including CD4+/CD8+ cells, were also significantly increased (p=0.0152). Affinity-isolated naturally processed myelin peptides were potent IFNγ stimulators for autologous PBMCs, but not for control PBMCs. Interpretation and conclusions: We show for the first time that myelin P0 is naturally processed in IgM MGUS B cells, acting as aberrant antigen-presenting cells in activation of patients T helper cells. Our findings cast new light on the important role of autoreactive P0-specific B cells in he induction of the pathogenic T cell responses found in nerve lesions of MGUS patients with peripheral neuropathy.
Nyckelord
- Monoclonal gammopathy of undetermined significance
- myelin P0
- peripheral neuropathy
- CD5+B cells
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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