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Coupled analysis of transcriptional states and somatic hypermutation in germinal center B cells reveals role for oxidative phosphorylation in positive selection

ABSTRACT: In this work we illustrate the power of coupling single cell analysis of transcriptional states with somatic hypermutation of germinal center B cells to reveal unanticipated roles of metabolic programs in the positive selection. We use massively parallel 5'-end scRNA-seq to simultaneously capture transcriptome states and mutation profiles of IgH variable genes in individual cells. Our computational analyses reveal that the OXPHOS module is enhanced in GC B cells undergoing positive selection in response to different antigens. Through deleting the Cox10 gene, which encodes a cytochrome oxidase assembly factor, specifically in GC B cells, we demonstrate that OXPHOS activity is required for cell division and positive selection. Furthermore, we show that chemical augmentation of OXPHOS activity facilitates the positive selection of GC B cells in vivo. Our findings therefore reveal that tuning of OXPHOS activity by increased affinity BCRs is critical for clonal expansion and positive selection.

ORGANISM(S): Mus musculus

PROVIDER: GSE154634 | GEO | 2021/04/16

REPOSITORIES: GEO

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