Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: In our previous work, we reported a link between interferon alpha inhibition and decreased expression of B cell activation genes in ex vivo whole blood samples from interferon kinoid-treated SLE patients. Here, we investigated the mechanisms underlying the effects of interferon alpha on B cell activation and differentiation.
Methods: PBMC and purified total (CD20+) or naïve (CD19+ CD20+ IgD+ CD27-) B cells were obtained from healthy controls and SLE patients. The effects of interferon alpha on B cell differentiation were studied by flow cytometry. STAT1 and STAT3 phosphorylation in CD20+ B cells (9 SLE and 5 control individuals) was evaluated by Western Blot. The role of STAT3 on B cell responses to interferon alpha was studied using pharmacological inhibitors (STA21 and S31201) and PBMC from STAT3-deficient individuals (n=5).
Results: Spontaneous levels of STAT3, but not STAT1, phosphorylation were significantly higher in total B cells from SLE patients compared to controls. In purified naïve B cells from controls, interferon alpha induced STAT1 and STAT3 phosphorylation. Interferon alpha also displayed direct stimulatory effects on purified naïve B cells from healthy individuals, as evidenced by a significant induction of cell surface CD38 and CD95 in the presence of the cytokine. Incubation of normal PBMC with interferon alpha induced a B cell differentiation pattern as observed spontaneously in SLE PBMC: decreased naïve, decreased unswitched memory, increased switched memory cells and increased plasmablasts. In addition, expression of cell surface CD95 was significantly induced by interferon alpha in all these B cell sub-populations, except in plasmablasts (unstimulated plasmablasts highly express CD95). Interferon alpha-induced B cell differentiation in total PBMC was significantly inhibited in the presence of STAT3 inhibitors, or in PBMC from STAT3-deficient patients.
Conclusion: Interferon alpha displays direct stimulatory effects on B cell differentiation and activation in SLE. STAT3 phosphorylation mediates the effects of interferon alpha stimulation in naïve B cells, an observation that opens new therapeutic perspectives in SLE.
To cite this abstract in AMA style:Ducreux J, Aleva F, Degroof A, Ferster A, van der Ven A, van de Veerdonk F, Houssiau FA, Lauwerys BR. STAT3 Phosphorylation Mediates the Stimulatory Effects of Interferon Alpha on B Cell Differentiation and Activation in SLE [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). http://acrabstracts.org/abstract/stat3-phosphorylation-mediates-the-stimulatory-effects-of-interferon-alpha-on-b-cell-differentiation-and-activation-in-sle/. Accessed May 25, 2018.
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