Immune complex–driven neutrophil activation and BAFF release: a link to B cell responses in SLE

OBJECTIVE: The role of neutrophils in driving pathogenic B cell responses in SLE is not fully understood. In this study, we explored the link between immune complex (IC)–driven neutrophil activation, the release of B cell pro-survival factor BAFF and B cell activation using SLE clinical samples. METHODS: BAFF levels were analysed in serum samples from patients with SLE (n=60) and healthy controls (HCs, n=20) by ELISA and correlated with markers of neutrophil activation and circulating IC levels. Neutrophils were stimulated with RNP/IgG ICs and neutrophil activation, the release of BAFF, and neutrophil-mediated B cell responses were studied in vitro. RESULTS: Levels of BAFF in patients with SLE were associated with markers of disease activity, including anti-dsDNA antibody titres (r=0.33, p<0.05), serum C3 levels (r=−0.57, p<0.001) and levels of circulating ICs (r=0.39, p<0.05). Stimulation of neutrophils from healthy individuals with RNP-ICs in vitro induced the release of BAFF (p<0.05), concomitant with formation of neutrophil extracellular traps (NETs) (p<0.05). In culture, neutrophils promoted B cell survival (p<0.05), proliferation (p<0.05) and CD27(hi)CD38(hi) plasmablast differentiation. CONCLUSIONS: Our results support a new mechanism by which ICs, on NET formation, induce the release of B cell pro-survival factor BAFF by neutrophils. Furthermore, neutrophils directly promoted B cell activation and cell differentiation. Targeting neutrophil–B cell interactions can be further explored as an approach for inhibiting pathogenic B cell responses in SLE.