B cell receptor signal transduction in the GC is short-circuited by high phosphatase activity. Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. T cell help controls the speed of the cell cycle in germinal center B cells. The microanatomic segregation of selection by apoptosis in the germinal center. We propose that elevated OXPHOS activity promotes B cell clonal expansion and also positive selection by tuning cell division times. Correspondingly, augmentation of OXPHOS activity with oltipraz promoted affinity maturation. Deletion of mitochondrial Cox10 in GC B cells resulted in reduced cell division and impaired positive selection. 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. Single-cell RNA sequencing and topic modeling revealed increased expression of the oxidative phosphorylation (OXPHOS) module in GC B cells undergoing mitoses. In spite of considerable progress, the genomic states underlying this process remain to be elucidated. The positive selection of GC B cells that acquire high-affinity mutations enables antibody affinity maturation. Antigen-activated B cells diversify variable regions of B cell antigen receptors by somatic hypermutation in germinal centers (GCs).
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