Session Title: B-cell Biology and Targets in Autoimmune Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose: Semaphorin3A (sem3A) and neuropilin-1 (NP-1), are important regulatory molecules, previously reported by us to play role in lupus glomerulonephritis. In a recent study we demonstrated that sema3A expression on B-regulatory cells (B-regs) of systemic lupus erythematosus (SLE) patients is significantly decreased when compared to that on B-regs of normal individuals. Aiming to achieve a better characterization of B-regs (previously identified by us as CD19+CD25highCD1dhighIL-10highTGF-βhigh), we asked whether other regulatory/stimulatory molecules are differently expressed on B-regs of SLE patients. We also asked whether the addition of sem3A into a culture of B cells could possibly immuno-modulate the expression of these molecules on B-regs.
Materials and Methods: The expression of CD72 and TGF-β (inhibitory molecules), and of CD100 (a stimulatory molecule) was assessed on B-regs of both normal individuals and SLE patients. We then added sema3A to cultured B cells and assessed their regulatory properties after 24 hours. Cell cycle analysis was also done in order to evaluate
Results: 1.The expression of both CD72 and TGF-β was significantly decreased (37.88%, 8.6%) and of CD100 (12.78%) on B-regs of SLE patients vs that on normal B-regs. (49.26%, 14.74%, 21.55% respectively; P=0.001)
2. Twenty four hours following the addition of sema3A to cultured B cells, a significant increase of TGF- β, CD72 and NP-1 molecules and decrease of CD100 on B-regs was noticed. However, this effect of sema3A on B cells was altered in SLE patients when compared to that of normal B cells.
Conclusion: 1. This is the first study were the above studied regulatory molecules are shown to be altered on B regs of SLE patients. 2. Sema3A enhances the regulatory properties of B regs, but this effect is also shown to be altered in SLE.
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