PD-L1+ Regulatory B Cells from Rheumatoid Arthritis Patients Have Impaired Function in Suppressing IFN-ү and IL-21 Production
Abstract
:1. Introduction
2. Results
2.1. B-Cell Subsets and PD-L1 Expression Are Differentially Distributed Among HCs and RA Patients
2.2. Expression of PD-1 on CD4+ Th and Treg Cells
2.3. Th and Treg Cell Proliferation Is Not Significantly Affected by PD-L1+ Breg Cells
2.4. Functional Analysis of PD-L1+ Breg Cells by Comparing Cytokine Production
3. Discussion
4. Methods
4.1. Patients and Controls
4.2. B and T Cell Isolation
4.3. Flow Cytometry and Cell Sorting
4.4. B and Th Cell Activation
4.5. Proliferation Assay
4.6. Evaluation of Cytokine Production
4.7. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
7AAD | 7-AminoactinomycinD |
ACPA | Anti-citrullinated protein antibody |
CFSE | Carboxyfluorescein diacetate Succinimidyl ester “mixed isomer” |
MACS | Magneticactivating cells sorting |
MB | Memory B cells |
PB | Plasma blast cells |
PBMCs | Peripheral blood mononuclear cells |
PC | Plasma B cells |
PD-1 | Programmed cell death protein 1 |
PMA | Phorbol 12-myristate 13-acetate |
RF | Rheumatoid factor |
Tfh | follicular T helper cells |
Tph | peripheral T helper cells |
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RA (n = 25) | Reference Value (RV) | |
---|---|---|
Age (y; mean [range]) | 63.60 (43–84) | — |
M/F (N) | 4/30 | — |
Disease duration (y; mean [range]) | 15.00 (4.00–29.00) | — |
Treatments: | ||
Methotrexate | 6 | — |
Methotrexate + folic acid | 1 | — |
Methotrexate + Medrol | 1 | — |
Methotrexate + Hydroxychloroquine | 2 | — |
Methotrexate + adalimumab-adaz | 1 | — |
Methotrexate + folic acid + Medrol | 1 | — |
Methotrexate + rituximab | 2 | — |
Methotrexate + Medrol + tofacitinib | 1 | — |
Certolizumab pegol + leflunomide | 1 | — |
Leflunomide + Medrol | 1 | — |
Leflunomide | 1 | — |
Etanercept + Leflunomide | 1 | — |
Adalimumab-adaz | 2 | — |
Sulfasalazine + Methotrexate + Adalimumab | 1 | — |
Adalimumab-adaz + hydroxychloroquine + Methotrexate + folic acid | 1 | — |
Methotrexate + folic acid + sulfasalazine + adalimumab-adaz | 1 | — |
Adalimumab + Methotrexate + folic acid + medrol+ hydroxychloroquine | 1 | — |
CRP (mg/L; mean [range]) | 12.30 (0.58–53.00) | <8 mg/L |
DAS28 [ESR-based] (mean [range]) | 4.00 (2.3–6.70.00) | |
aCCP (IU/mL) | <20 IU/mL | |
aCCP − | n = 5 | |
aCCP + (mean [range]) | 2161.00 (25.00–32,000.00) | |
RF (IU/mL) | <20 IU/mL | |
RF − | n = 8 | |
RF + (mean[range]) | 151.85 (13.00–961.00) |
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Talib, M.; Gyebrovszki, B.; Fodor, A.; Mészáros, A.; Balog Virág, K.; Barta, L.G.; Rojkovich, B.; Nagy, G.; Sármay, G. PD-L1+ Regulatory B Cells from Rheumatoid Arthritis Patients Have Impaired Function in Suppressing IFN-ү and IL-21 Production. Int. J. Mol. Sci. 2025, 26, 2998. https://doi.org/10.3390/ijms26072998
Talib M, Gyebrovszki B, Fodor A, Mészáros A, Balog Virág K, Barta LG, Rojkovich B, Nagy G, Sármay G. PD-L1+ Regulatory B Cells from Rheumatoid Arthritis Patients Have Impaired Function in Suppressing IFN-ү and IL-21 Production. International Journal of Molecular Sciences. 2025; 26(7):2998. https://doi.org/10.3390/ijms26072998
Chicago/Turabian StyleTalib, Mustafa, Balázs Gyebrovszki, Anna Fodor, Anna Mészáros, Kata Balog Virág, Leila Gloria Barta, Bernadette Rojkovich, György Nagy, and Gabriella Sármay. 2025. "PD-L1+ Regulatory B Cells from Rheumatoid Arthritis Patients Have Impaired Function in Suppressing IFN-ү and IL-21 Production" International Journal of Molecular Sciences 26, no. 7: 2998. https://doi.org/10.3390/ijms26072998
APA StyleTalib, M., Gyebrovszki, B., Fodor, A., Mészáros, A., Balog Virág, K., Barta, L. G., Rojkovich, B., Nagy, G., & Sármay, G. (2025). PD-L1+ Regulatory B Cells from Rheumatoid Arthritis Patients Have Impaired Function in Suppressing IFN-ү and IL-21 Production. International Journal of Molecular Sciences, 26(7), 2998. https://doi.org/10.3390/ijms26072998