TY - JOUR T1 - Immune complex–driven neutrophil activation and BAFF release: a link to B cell responses in SLE JF - Lupus Science & Medicine JO - Lupus Sci Med DO - 10.1136/lupus-2022-000709 VL - 9 IS - 1 SP - e000709 AU - Ting Wang AU - Andrew Vasconcellos AU - John Marken AU - Sladjana Skopelja-Gardner AU - Christian Lood AU - Natalia V Giltiay Y1 - 2022/07/01 UR - http://lupus.bmj.com/content/9/1/e000709.abstract N2 - 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 CD27hiCD38hi 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. ER -