Session Type: Abstract Submissions (ACR)
Background/Purpose: Several studies linked the emergence of autoimmunity to abnormalities of the B-cell receptor (BCR) due to disturbances of signaling molecules or its co-receptors. Therefore this study focused on spleen tyrosine kinase (Syk), a key molecule of early BCR signaling in autoimmunity. Our model is systemic lupus erythematosus (SLE) which 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.
Methods: Peripheral blood was taken from 31 healthy, 61 SLE patients, 15 patients with rheumatoid arthritis (RA) and 16 primary Sjögren’s syndrome (pSS) patients. The expression of Syk and basal / BCR-induced phosphorylation of Syk by B-cells were studied by phosphoflow analysis. To assess the localization of Syk within B-cells, immunofluorescence was performed and analyzed by confocal microscopy. In addition, characterization of B-cells was evaluated by flow cytometry using the following markers CD19, CD20, CD27, CD38, IgD, CD95 and Ki67. Finally, the capacity of B-cells to differentiate into antibody producing cells was evaluated by flow cytometry and Elispot after 5 days of in vitro culture.
Results: In this study, two different subsets according their expression of Syk (Sykbright and Sykdim) within the CD20+CD27(-) population have been identified. The frequency of CD27(-)Sykbright B-cells were significantly increased in SLE compare to HD, however the disease activity (SLEDAI) do not correlate with the frequency of this subset. No significant increase in the frequency of this population was observed in others autoimmune diseases (i.e. RA and pSS). This subset showed an accumulation of Syk within the cytoplasm, a superior response to the BCR and plasma cell differentiation compared to CD27(-) Sykdim B-cells. Finally, this subset exhibited a memory-like phenotype.
Conclusion: A novel subset of B-cells defined as CD27(-)Sykbright B-cells and carrying memory features has been identified in SLE patients. This population represents a prime candidate how peripheral check point control of conventional B cells can be possibly bypassed in SLE.
S. J. Fleischer,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-novel-cd27-b-cell-subset-identified-based-on-intracellular-characteristics-is-expanded-in-sle/