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

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Abstract

Germinal center (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, combining imaging, molecular, and genomic approaches, we defined 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 GCs in the salivary glands of Sjögren’s disease, defining its role in autoimmunity.

Authors

Marta C. Sallan, Filip Filipsky, Christina H. Shi, Elena Pontarini, Manuela Terranova-Barberio, Gordon Beattie, Andrew Clear, Michele Bombardieri, Kevin Y. Yip, Dinis Pedro Calado, Mark S. Cragg, Sonya James, Mathew Carter, Jessica Okosun, John G. Gribben, Tanya Klymenko, Andrejs Braun