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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE218050 | GEO | 2025/05/12

REPOSITORIES: GEO

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

Project description: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.

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