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.
Keywords: B-lymphocytes; autoantibodies; cytokines; lupus erythematosus, systemic.
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.