The extrafollicular response is sufficient to drive initiation of autoimmunity and early disease hallmarks of lupus

Many autoimmune diseases are characterized by germinal center (GC)-derived, affinity-matured, class-switched autoantibodies, and strategies to block GC formation and progression are currently being explored clinically. However, extrafollicular responses can also play a role. The aim of this study was to investigate the contribution of the extrafollicular pathway to autoimmune disease development. We blocked the GC pathway by knocking out the transcription factor Bcl-6 in GC B cells, leaving the extrafollicular pathway intact. We tested the impact of this intervention in two murine models of systemic lupus erythematosus (SLE): a pharmacological model based on the chronic epicutaneous application of the Toll-like receptor (TLR)-7 agonist Resiquimod (R848), and 564Igi autoreactive B cell receptor knock-in mice. The B cell-intrinsic effects were further investigated in vitro and in autoreactive mixed bone marrow chimeras. GC block failed to curb autoimmune progression in the R848 model base..., Please see the README document (\"README_file extrafollicular response is sufficient paper Voss LF et al 2022\") and the accompanying published article: Voss LF et al. 2022. The extrafollicular response is sufficient to drive initiation of autoimmunity and early disease hallmarks of lupus. Frontiers in Immunology. Accepted. DOI: 10.3389/fimmu.2022.1021370,