Autophagy is an upstream mediator of chromatin dynamics in normal and autoimmune germinal center B cells
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
- Sonya James (ORCID: https://orcid.org/0000-0002-0032-5935)
- Gordon Beattie
- Elena Pontarini (ORCID: https://orcid.org/0000-0003-0439-0344)
- Dinis Pedro Calado (ORCID: https://orcid.org/0000-0001-8239-7184)
- Matthew J. Carter (ORCID: https://orcid.org/0000-0002-5198-5933)
- Andrejs Braun (ORCID: https://orcid.org/0000-0003-0925-5598)
- Filip Filipsky (ORCID: https://orcid.org/0000-0002-4357-4464)
- Tetyana Klymenko (ORCID: https://orcid.org/0000-0001-8029-3082)
- Jessica Okosun (ORCID: https://orcid.org/0000-0001-6021-5044)
- Kevin Y. Yip (ORCID: https://orcid.org/0000-0001-5516-9944)
- John G. Gribben (ORCID: https://orcid.org/0000-0002-8505-7430)
- Mark Steven Cragg (ORCID: https://orcid.org/0000-0003-2077-089X)
- Marta C. Sallán (ORCID: https://orcid.org/0000-0002-5781-3059)
- Chaojing Shi (ORCID: https://orcid.org/0009-0007-7595-5556)
- Andrew Clear (ORCID: https://orcid.org/0000-0001-8246-5642)
- Stefano Bombardieri (ORCID: https://orcid.org/0000-0002-3878-5216)
- Manuela Terranova-Barberio
Institutions
- Queen Mary University of London (GB)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Discovery Institute (US)
- The Francis Crick Institute (GB)
- Genomics England (GB)
- William Harvey Research Institute (GB)
- University of Southampton (GB)
- University College London (GB)
Publication Details
- Journal
- Journal of Clinical Investigation
- Published
- 2025-05-15
- DOI
- https://doi.org/10.1172/jci178920
- Citations
- 3
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 2.39
Funders
- Wellcome Trust
- Francis Crick Institute
- Cancer Research UK
- National Institute for Health and Care Research
- University College London
- Blood Cancer UK
- Medical Research Council