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B cells as a therapeutic target for IFN-β in relapsing-remitting multiple sclerosis
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 186(7)
- Publication Year :
- 2011
-
Abstract
- IFN-β-1b is a first-line immunomodulatory therapy for relapsing–remitting multiple sclerosis (RR MS). However, its effects on B cells have not been characterized. In vitro studies of B cells derived from RR MS patients revealed that IFN-β-1b decreases B cells’ stimulatory capacity, as detected by inhibition of the Ag-specific T cell proliferative response upon Ag presentation by IFN-β-1b–treated B cells. Our study has identified that IFN-β-1b inhibited B cells’ stimulatory capacity in RR MS patients and healthy controls through the suppression of CD40 and CD80 expression, whereas the MHC class I and II expression was not changed. IFN-β-1b in vitro treatment inhibited B cell secretion of IL-1β and IL-23 and induced IL-12 and IL-27. Supernatants transferred from IFN-β-1b–treated B cells inhibited Th17 cell differentiation, as they suppressed gene expression of the retinoic acid-related orphan nuclear hormone receptor C and IL-17A and secretion of IL-17A. In addition, IFN-β-1b induced B cells’ IL-10 secretion, which may mediate their regulatory effect. Studies of B cells derived from RR MS patients treated with recombinant s.c. injected IFN-β-1b revealed that they induced a significantly lower proliferative response in allogenic MLR than the B cells from untreated patients. Further confirming the IFN-β-1b in vitro-induced changes in B cell cytokine secretion, B cells derived from the IFN-β-1b–treated patients secreted significantly lower levels of IL-1β and IL-23 and higher levels of IL-12 and IL-27 in comparison with the B cells derived from untreated patients. We conclude that IFN-β-1b exerts its therapeutic effects in part by targeting B cells’ functions that contribute to the autoimmune pathogenesis of RR MS.
- Subjects :
- medicine.medical_specialty
T cell
Cellular differentiation
Immunology
Interleukin-1beta
B-Lymphocyte Subsets
Biology
Interleukin-23
Atacicept
Drug Delivery Systems
Multiple Sclerosis, Relapsing-Remitting
Adjuvants, Immunologic
Internal medicine
medicine
Immunology and Allergy
Humans
B cell
Cells, Cultured
CD40
Interferon beta-1a
Dendritic Cells
Interferon-beta
medicine.disease
Molecular biology
Coculture Techniques
Endocrinology
medicine.anatomical_structure
biology.protein
Cytokine secretion
Lymphocyte Culture Test, Mixed
CD80
medicine.drug
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 186
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....52642f36c3982c7375fcc509c8dee294