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

ABSTRACT:

Introduction

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.

Methods

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 chronic epicutaneous application of the Toll-like receptor (TLR)-7 agonist Resiquimod (R848), and

SUBMITTER: Voss LF 

PROVIDER: S-EPMC9795406 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature