Background/Purpose: Beyond their antibody producing function, B cells have been shown to be potent antigen-presenting and cytokine-producing cells. In systemic lupus erythematosus (SLE), B cells have been reported to be hyper-reactive, but it is not entirely known how cytokine production changes. An important signaling mechanism in B cell hyper-reactivity is Toll-like receptor 9 (TLR-9), which is up-regulated in B cells from patients with active SLE. Therefore, the aim of this study was to profile the cytokine production by B cells upon TLR-9 activation and to compare healthy donors (HD) to SLE-patients. In addition, the capacities of B cells to produce cytokines were put in relation with disease activity (SLEDAI) and serum autoantibody titers.

Methods: Untouched B cells from 19 SLE-patients and 13 HD were purified from peripheral blood mononuclear cells and were stimulated in vitro using CpG for 48 hours. The culture supernatants were harvested and then tested for 28 cytokines and chemokines by Bio-Plex. The cytokine responses upon stimulation were compared between both groups and correlated with the SLEDAI and anti-dsDNA titers for SLE-patients.

Results: 24 out of 28 cytokines/chemokines measured were significantly up-regulated upon TLR-9 stimulation compared to un-stimulated B cells (p<0.05). Although B cells from SLE patients showed a trend to produce less cytokine than B cells from HD, no significant differences were observed. However, the amount of IL-2, IL-4, IL-7, IL-12p70, IL13, IL-15, IL-17A, Eotaxin, Basic FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MIP-1α, and VEGF produced by B cells from SLE-patients inversely correlated with their SLEDAI (p<0.05) and even more (additionally IL-1β, IL-1ra, MIP-1β and TNF-α) with their anti-dsDNA antibody titers. Interestingly, the more CD27⁺ memory B cells were in the cells culture from SLE-patients, the more IP-10 and TNF-α were produced.

Conclusion: This study highlighted unknown perturbations of cytokine/chemokine production by B cells in active SLE upon TLR-9 stimulation with an inverse correlation of cytokines/chemokines produced by B cells with SLEDAI and anti-dsDNA titers. Most prominent were pro-inflammatory mediators as IP-10, MIP-1α, TNF-α, and VEGF. This suggests that the known enhanced B cell proliferation and differentiation upon TLR9-stimulation possibly results in a diminished cytokine production.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/profiling-cytokine-production-of-b-cells-from-sle-patients-upon-tlr9-stimulation/