Autophagy is an upstream mediator of chromatin dynamics in normal and autoimmune germinal centre B cells.

Abstract

Germinal centre (GC) B cells are pivotal in establishing a robust humoral immune response and long-term serological immunity while maintaining antibody self-tolerance. GC B cells rely on autophagy for antigen presentation and homeostatic maintenance. However, these functions, primarily associated with the light zone, cannot explain the spatiotemporal autophagy upregulation in the dark zone of GCs. Here, we define a functional mechanism controlling chromatin accessibility in GC B cells during their dark zone transition. This mechanism links autophagy and nuclear Lamin B1 dynamics with their downstream effects, including somatic hypermutation and antibody affinity maturation. Moreover, the autophagy-Lamin B1 axis is highly active in the aberrant ectopic germinal centres in the salivary glands of Sjogren's disease, defining its role in autoimmunity.