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Autophagy controls DNA accessibility to immunoglobulin variable regions and centroblast dynamics [scRNA-seq]

GSE218051 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/05/12 Platform GPL19057
Summary
Nuclear lamina dynamic changes influence chromatin landscape. Mechanisms governing nuclear lamina behavior have not been studied within the adaptive immune context. Here, we show autophagy regulates withdrawal of nuclear lamina protein, Lamin B1, in B cells transiting germinal centers (GCs). Autophagy inhibition was sufficient to keep Lamin B1 nuclear integrity preventing NP-CGG immunisation-induced nucleotide substitution during the somatic hypermutation process resulting in compromised B cell capacity to build up a competitive high-affinity antibodies. Atg7 loss-of-function in GC B cells resolved in decreased chromatin accessibility. Single-cell RNAseq revealed centroblasts accumulate in dark zone upon autophagy impairment due to inefficient signals to finish GC reaction. Hence, GC B cells rely on autophagy for Lamin B1 disassembly, becoming autophagy key part of somatic hypermutation process and centroblast dynamics.
Published in
Autophagy is an upstream mediator of chromatin dynamics in normal and autoimmune germinal center B cells
Sallan MC, Filipsky F, Shi CH et al. · The Journal of clinical investigation 2025 · PMID 40397664 · doi:10.1172/JCI178920
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Also filed as BioProject PRJNA901991 and SRA study SRP408110. Searching any of these in the dataset finder brings you back here.

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