Coupled Analysis of Transcriptome and BCR Mutations Reveals Role of OXPHOS in Affinity Maturation

Overview

Journal Nat Immunol

Date 2021 May 25

PMID 34031613

Citations 49

Authors

Dianyu Chen

Yan Wang

Godhev K Manakkat Vijay

Shujie Fu

Colt W Nash

Di Xu

Danyang He

Nathan Salomonis

Harinder Singh

Heping Xu

Affiliations

Soon will be listed here.

Abstract

Antigen-activated B cells diversify variable regions of B cell antigen receptors by somatic hypermutation in germinal centers (GCs). The positive selection of GC B cells that acquire high-affinity mutations enables antibody affinity maturation. In spite of considerable progress, the genomic states underlying this process remain to be elucidated. Single-cell RNA sequencing and topic modeling revealed increased expression of the oxidative phosphorylation (OXPHOS) module in GC B cells undergoing mitoses. Coupled analysis of somatic hypermutation in immunoglobulin heavy chain (Igh) variable gene regions showed that GC B cells acquiring higher-affinity mutations had further elevated expression of OXPHOS genes. Deletion of mitochondrial Cox10 in GC B cells resulted in reduced cell division and impaired positive selection. Correspondingly, augmentation of OXPHOS activity with oltipraz promoted affinity maturation. We propose that elevated OXPHOS activity promotes B cell clonal expansion and also positive selection by tuning cell division times.

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