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42. Kongress der Deutschen Gesellschaft für Rheumatologie, 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 24. Wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

17.-20. September 2014, Düsseldorf

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A novel CD27(-) memory B-cell subset identified based on intracellular characteristics is expanded in SLE

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  • Sarah Fleischer - Deutsches Rheuma-Forschungszentrum (DRFZ), Charité - Universitätsmedizin Berlin Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Capucine Daridon - Deutsches Rheuma-Forschungszentrum (DRFZ), Charité - Universitätsmedizin Berlin Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Thomas Dörner - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Düsseldorf, 17.-20.09.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocER.21

doi: 10.3205/14dgrh167, urn:nbn:de:0183-14dgrh1671

Published: September 12, 2014

© 2014 Fleischer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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Background: Systemic lupus erythematosus (SLE) is an autoimmune disease known to be associated with a breakdown of self-tolerance resulting in auto-antibody production, B-cell hyper-reactivity and disturbed B-cell homeostasis of peripheral B-cell subsets. To analyze more in detail to which extend the BCR key downstream spleen tyrosine kinase (Syk) contributes to B-cell abnormalities in SLE, comprehensive functional and phenotypic analyses on SLE B-cells were performed.

Methods: B-cells from healthy donors (HD) and SLE patients were analyzed by flow cytometry to assess basal expression of Syk and phosphorylated (p-)Syk. Different B-cell subsets regarding their Syk and CD27 expression were characterized for CD19, CD20, CD38, IgD, IgM, CD95, Ki67 and their ABC-B1 transporter activity. In addition, in vitro studies analyzed the differentiation potential of CD27(-)Syk++ B-cells into IgG secreting plasma-cells and the induction of Syk by cytokines.

Results: In this study, two different subsets according their expression of Syk (Syk++ and Syk+) within the CD20+CD27(-) population have been identified. The frequency of CD27(-)Syk+ B-cells were significantly increased in SLE compare to HD, however the disease activity (SLEDAI) do not correlate with the frequency of this subset. A substantially increased Syk and basal p-Syk expression as well as an increased cytoplasmic Syk accumulation was found in CD27(-)Syk++ compared to CD27(-)Syk+ B-cells. Furthermore, phenotypical characterization identified CD27(-)Syk++ B-cells as CD19++, CD20++, mainly CD21(-) and CD38(-) with decreased ABC-B1 transporter activity representing a memory phenotype. CD27(-)Syk++ B-cells showed hypermutated Ig genes as well as an enhanced differentiation into IgG secreting plasma-cells in contrast to CD27(-)Syk+ cells. Finally, in vitro stimulation with IFN-γ and LPS induced the emergence of Syk++ B-cells.

Conclusion: In conclusion, SLE patients exhibit an increased frequency of a novel CD27(-)Syk++ subset of B-cells with memory features. Therefore, the current study provides evidence that the use of intracellular markers, such as Syk, permits improved distinction of naïve and memory B-cell subsets.