Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic lupus erythematosus (SLE) is characterized by an expanded population of peripheral memory B cells. However, little is known about the qualitative abnormality of B cells associated with the pathogenesis of SLE. We assessed the subset of B cells by expression of chemokine receptors in patients with SLE and performed in vitro analysis to assess the differentiation mechanisms of those subsets.
Methods: PBMCs obtained from subjects with 56 patients with SLE, 31 patients with rheumatoid arthritis (RA) and 20 healthy donors (HD) were analyzed. Circulating B cell subsets were categorized by expression of chemokine receptors such as CXCR3 and CXCR5. Additionally, pan B cells obtained from HDs were cultured 4 days under stimulation with B cell receptor, co-stimulatory molecules and cytokines such as IL-21 and type I/II interferons (IFNs), and we assessed the expression of chemokine receptors such as CXCR3 and CXCR5 and transcription factors such as T-bet and Bcl-6 by multi-color flow cytometry.
Results: 1) The proportion of effector memory B cells (EM B cells; CD19+CD20+IgD–CD27–) has significantly increased in SLE compared to HD and RA (p<0.01). 2) The proportion of CD19+CD20+CXCR5–CXCR3– B cells and CD19+CD20+ CXCR5–CXCR3+ B cells has significantly increased in SLE, compared to HD and RA, which were remarkably noted in CD19+CD20+IgD–CD27+/- memory B cells (p<0.01). 3) CXCR5 expression was decreased in cultured B cells stimulated by BCR, CD40 ligands and IFN-β (p<0.05). By contrast, CXCR3 expression was increased in cultured B cells stimulated by BCR, CD40 ligands and IFN-γ (p<0.05). 4) T-bet expression was increased in cultured B cells stimulated by BCR, CD40 ligands and IFN-γ (p<0.05).
Conclusion: The results indicated that abnormality of B cell in SLE is characterized by not only quantitative increase in peripheral memory B cells but also unique expression pattern of chemokine receptors with down-regulation of CXCR5 and up-regulation of CXCR3 in EM B cells, indicating a potential of preferential migration into peripheral organs. Furthermore, in vitro experiments revealed that type I/II IFNs are a potent inducer of EM B cells involving abnormal chemokine receptor expression, suggesting an importance of these cytokines for the pathogenesis of SLE.
To cite this abstract in AMA style:Yoshikawa M, Nakayamada S, Kubo S, Iwata S, Sakata K, Miyazaki Y, Nakano K, Saito K, Tanaka Y. Type I/II Interferon Commits to Abnormal Expression of Chemokine Receptor on B Cells in Patients with Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/type-iii-interferon-commits-to-abnormal-expression-of-chemokine-receptor-on-b-cells-in-patients-with-systemic-lupus-erythematosus/. Accessed September 21, 2019.
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