Session Information
Title: B cell Biology and Targets in Autoimmune Disease: Systemic Lupus Erythematosus and Related Diseases
Session Type: Abstract Submissions (ACR)
Background/Purpose: Systemic lupus erythematosus (SLE) is an autoimmune disease known to be associated with a breakdown of self-tolerance, B-cell hyperactivity and disturbed B-cell homeostasis of peripheral B-cell subsets. To analyze in more detail the extent to which the B- cell antigen receptor (BCR) proximal 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. B-cell subsets expressing distinct levels of Syk were identified and characterized phenotypically by flow cytometry, microscopy and molecularly to assess IgVH rearrangements. Their functions were analyzed by in vitrodifferentiation assays into plasma-cells and Syk induction by cytokines.
Results: A significantly increased frequency of CD27(-) B-cells with enhanced expression of Syk (Syk++) was found specifically in SLE patients. CD27(-)Syk++ B-cells showed a substantially increased Syk and basal p-Syk expression as well as an increased cytoplasmic Syk accumulation and increased Syk phosphorylation upon BCR engagement compared to CD27(-)Syk+ B-cells. Furthermore, CD27(-)Syk++ B-cells were characterized as CD38(-) as well as CD19++, CD20++ and mainly CD21(-) with reduced ABC-B1 transporter activity and exhibited somatically mutated IgVH rearrangements. CD27(-)Syk++ B-cells showed an enhanced differentiation into IgG secreting plasma-cells in contrast to CD27(-)Syk+ cells. Finally, Syk++ B-cells were inducible in vitro by stimulation with IFN-γ, LPS or TNF-α.
Conclusion: SLE patients exhibit an increased frequency of a novel CD27(-)Syk++ subset of B-cells with memory B-cell characteristics which candidate as a source of increased plasma-cells characteristic of SLE patients. Moreover, the evidence indicates that the use of intracellular markers, such as Syk, permitted a distinction between naïve and memory B-cell subsets within the CD27(-) B-cells and and a more precise delineation of the CD27(-) memory B-cell subset.
Disclosure:
S. Fleischer,
None;
C. Giesecke,
None;
H. Mei,
None;
P. E. Lipsky,
None;
C. Daridon,
None;
T. Dörner,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-novel-cd27-spleen-tyrosine-kinase-syk-bright-memory-b-cell-subset-is-expanded-in-sle/