Zuzana Parackova1, Adam Klocperk2, Michal Rataj3, Jana Kayserova4, Irena Zentsova5, Zdenek Sumnik6, Stanislava Kolouskova7, Jana Sklenarova8, Stepanka Pruhova9, Barbora Obermannova10, Lenka Petruzelkova11, Jan Lebl12, Tomas Kalina13, Anna Sediva14. 1. Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: zuzana.parackova@fnmotol.cz. 2. Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: adam.klocperk@fnmotol.cz. 3. Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: michal.rataj@fnmotol.cz. 4. Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: jana.kayserova@lfmotol.cuni.cz. 5. Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: irena.zentsova@fnmotol.cz. 6. Department of Pediatrics, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: zdenek.sumnik@lfmotol.cuni.cz. 7. Department of Pediatrics, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: stanislava.kolouskova@lfmotol.cuni.cz. 8. Department of Pediatrics, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: jana.sklenarova@fnmotol.cz. 9. Department of Pediatrics, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: stepanka.pruhova@fnmotol.cz. 10. Department of Pediatrics, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: barbora.obermannova@fnmotol.cz. 11. Department of Pediatrics, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: lenka.petruzelkova@fnmotol.cz. 12. Department of Pediatrics, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: an.lebl@lfmotol.cuni.cz. 13. Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: tomas.kalina@lfmotol.cuni.cz. 14. Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic. Electronic address: anna.sediva@fnmotol.cz.
Abstract
BACKGROUND: Lately, mounting evidence has shown that B cells play an important role in the pathogenesis of type 1 diabetes (T1D). Here, we present alterations in B cell subsets including BAFF receptor (BAFFR) expression in cohorts of patients with type 1 diabetes (T1D) and their relatives. PATIENTS AND METHODS: B cells were studied in 438 patients with T1D (158 at disease onset and 280 with long-term disease), 136 first-degree relatives and 53 healthy controls. The B cell panel included transitional, naïve, MZ-like, switched memory B cells and plasmablasts. We also measured serum BAFF levels as well as BAFFR expression on both B and T cells. Moreover, the effect of BAFF on T and B lymphocytes was analysed in vitro. RESULTS: We observed a significant decrease in the proportion of transitional B cells in the patients with T1D, accompanied by an increased proportion of plasmablasts, especially in recent-onset patients and their relatives. While the BAFF serum levels did not differ in the patients with T1D, BAFFR-expressing B and especially T cell numbers were reduced in the T1D cohort, with the exception of patients with recent-onset disease who exhibited a significant increase in the number of BAFFR-expressing T cells. T cell activation and B cell proliferation were more pronounced after activation with BAFF in the T1D cohort compared to controls. CONCLUSION: The B cell panel in patients with T1D is characterized by significantly reduced populations of B cells in their early stages of development with a shift towards plasma cells. The dynamics of BAFFR-expressing B and T cells and the more pronounced responsiveness of the T1D T cells to BAFF point to the role of BAFF and T and B cell cooperation in the development of T1D.
BACKGROUND: Lately, mounting evidence has shown that B cells play an important role in the pathogenesis of type 1 diabetes (T1D). Here, we present alterations in B cell subsets including BAFF receptor (BAFFR) expression in cohorts of patients with type 1 diabetes (T1D) and their relatives. PATIENTS AND METHODS: B cells were studied in 438 patients with T1D (158 at disease onset and 280 with long-term disease), 136 first-degree relatives and 53 healthy controls. The B cell panel included transitional, naïve, MZ-like, switched memory B cells and plasmablasts. We also measured serum BAFF levels as well as BAFFR expression on both B and T cells. Moreover, the effect of BAFF on T and B lymphocytes was analysed in vitro. RESULTS: We observed a significant decrease in the proportion of transitional B cells in the patients with T1D, accompanied by an increased proportion of plasmablasts, especially in recent-onset patients and their relatives. While the BAFF serum levels did not differ in the patients with T1D, BAFFR-expressing B and especially T cell numbers were reduced in the T1D cohort, with the exception of patients with recent-onset disease who exhibited a significant increase in the number of BAFFR-expressing T cells. T cell activation and B cell proliferation were more pronounced after activation with BAFF in the T1D cohort compared to controls. CONCLUSION: The B cell panel in patients with T1D is characterized by significantly reduced populations of B cells in their early stages of development with a shift towards plasma cells. The dynamics of BAFFR-expressing B and T cells and the more pronounced responsiveness of the T1D T cells to BAFF point to the role of BAFF and T and B cell cooperation in the development of T1D.
Authors: Wendy E Powell; Stephanie J Hanna; Claire N Hocter; Emma Robinson; Joanne Davies; Gareth J Dunseath; Stephen Luzio; Daniel Farewell; Li Wen; Colin M Dayan; David A Price; Kristin Ladell; F Susan Wong Journal: Diabetologia Date: 2018-06-07 Impact factor: 10.122