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Marginal-Zone B-Cells Are Main Producers of IgM in Humans, and Are Reduced in Patients With Autoimmune Vasculitis
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.ORCID iD: 0000-0002-3555-7162
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Lund Univ, Sweden; Skane Univ Hosp, Sweden.
2018 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 2242Article in journal (Refereed) Published
Abstract [en]

In mice, B1 and marginal zone (MZ) B-cells play an important role in prevention of autoimmunity through production of regulatory cytokines and natural antibodies. There is limited knowledge about the human counterparts of these cells. We therefore investigated functions of MZ-like B-cells and the frequency of circulating MZ-like and Bl-like B-cells in healthy controls (HC), as well as in patients with autoimmune vasculitis to learn more about the role of these cells in autoimmune disease. After stimulation with CpG oligodeoxynucleotides (ODN) of class B in vitro, MZ-like B-cells were the main producers of IgM whereas switched memory B-cells primarily produced IgG and IgA. TNF and IL-10 were produced by both MZ-like and switched memory B-cells. Neither antibody nor TNF/IL-10 production by the B-cell subsets differed between patients and HC. Patients with autoimmune vasculitis, irrespective of disease activity, had lower percentage and absolute numbers of circulating MZ-like B-cells, and lower absolute numbers of B1-like B-cells. The percentage of B1-like B-cells was reduced during active disease. These findings remained significant when the analysis was confined to active treatment-naive patients (disease onset).Our results suggest that human innate-like B-cells might have a physiological role in prevention of autoimmunity.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2018. Vol. 9, article id 2242
Keywords [en]
marginal-zone (MZ) B-cells; B1 B-cells; innate-like B-cells; natural antibodies; T-cell-independent antibodies; IgM; autoimmunity; anti-neutrophil cytoplasmic autantibody (ANCA) associated vasculitis
National Category
Immunology
Identifiers
URN: urn:nbn:se:liu:diva-152056DOI: 10.3389/fimmu.2018.02242ISI: 000446095400001OAI: oai:DiVA.org:liu-152056DiVA, id: diva2:1259444
Note

Funding Agencies|Ingrid Asps Foundation; Swedish Society of Nephrology; Swedish Renal Foundation

Available from: 2018-10-29 Created: 2018-10-29 Last updated: 2018-12-04

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Appelgren, DanielEriksson, PerErnerudh, JanSegelmark, Mårten
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Division of Drug ResearchFaculty of Medicine and Health SciencesDivision of Neuro and Inflammation ScienceDepartment of RheumatologyDepartment of Clinical Immunology and Transfusion MedicineDepartment of Nephrology
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