Artikel
BTLA expression is reduced in SLE B cells and controls plasmacytosis
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Autoren
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Ana-Luisa Stefanski
- Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité Berlin, Berlin; Deutsches Rheuma Forschungszentrum, Berlin
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Annika Wiedemann
- Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité Berlin, Berlin; Deutsches Rheuma Forschungszentrum, Berlin
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Marie Lettau
- Charité Berlin, Funktionelle Anatomie, Berlin
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Eva Schrezenmeier
- Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité Berlin, Berlin; Deutsches Rheuma Forschungszentrum, Berlin; Charité, Medizinische Klinik mit Schwerpunkt Nephrologie, Berlin
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Hector Rincon-Arevalo
- Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité Berlin, Berlin; Deutsches Rheuma Forschungszentrum, Berlin; Charité, Medizinische Klinik mit Schwerpunkt Nephrologie, Berlin; Medellín, Facultad de Medicina, Instituto de Investigaciones Médicas, Medellín
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Karin Reiter
- Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité Berlin, Berlin; Deutsches Rheuma Forschungszentrum, Berlin
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Tobias Alexander
- Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité Berlin, Berlin
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Falk Hiepe
- Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité Berlin, Berlin
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Andreia C. Lino
- Deutsches Rheuma Forschungszentrum, Berlin
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Thomas Dörner
- Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité Berlin, Berlin; Deutsches Rheuma Forschungszentrum, Berlin
| Veröffentlicht: | 14. September 2021 |
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Gliederung
Text
Introduction: B- and T-lymphocyte attenuator (BTLA/CD272) is an inhibitory co-receptor constitutively expressed on B cells [1] that negatively regulates BCR signaling [2]. Prior studies reported defective function of BTLA by T cells in patients with systemic lupus erythematosus (SLE) [3], however, data on BTLA expression and function for B cells in autoimmunity is missing.
Methods: Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors (HD) and 34 SLE patients were stained for BTLA and its expression on B cells was assessed. PBMCs or CD27-IgD+ naive B cells were stimulated together with an activating anti-BTLA antibody or an inhibitor of spleen tyrosine kinase (SYK) and B cell memory induction and plasmablast differentiation were analyzed. Significance was tested by Wilcoxon signed rank test for paired comparisons and Mann Whitney U test for comparison of unpaired samples. Correlation of BTLA expression and clinical disease markers was assessed by Spearman’s rank correlation. Differences with a P value < 0.05 were considered statistically significant.
Results: Analysis of BTLA surface expression on B cell subsets in SLE patients and HD revealed reduced BTLA expression on CD27-IgD+ naïve B cells from SLE patients (p=0.0017, Figure 1A [Fig. 1]). Remarkably, an inverse correlation was found for BTLA expression on naïve SLE B cells with anti-dsDNA antibody titers (p=0.0394) and Siglec-1 expression on monocytes, a marker for interferon signature (p=0.0196). BTLA engagement was found to control CpG/TLR9 activation limiting plasmablast (p=0.0156) and B cell memory induction (p=0.0078) in HD B cells (Figure 1B [Fig. 1]). These BTLA functions were impaired in SLE B cells (Figure 1C [Fig. 1]). Reduced BTLA expression and function of naive SLE B cells could be overcome by SYK inhibition.
Conclusion: Herein, we document that B cell subsets of SLE patients express lower levels of the inhibitory checkpoint regulator BTLA than HD. This impaired inhibitory activity seems to play a role regarding B cell memory differentiation and plasmocytosis in SLE pathophysiology, suggesting that BTLA can be a therapeutic target in SLE.
Disclosures: Annika Wiedemann, Ana-Luisa Stefanski, Marie Lettau, Eva-Vanessa Schrezenmeier, Hector Rincon-Arevalo, Karin Reiter, Tobias Alexander, Falk Hiepe, Andreia Lino: None declared; Thomas Dörner Grant/research support from: Eli Lilly, Janssen, Roche, UCB Pharma, Consultant for: Eli Lilly, Janssen, Roche, UCB Pharma, Speakers bureau: Eli Lilly, Janssen.
Ana-Luisa Stefanski wird von der DGRh Forschungsförderung über das Kompetenznetz Rheuma unterstützt.
References
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