Epi-microRNA mediated metabolic remodelling ensures affinity maturation

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Germinal center (GC)-B cell proliferation relies on oxidative phosphorylation. Positively selected GC-B cells initiate cell division in the hypoxic light zone (LZ) microenvironment and continue vigorous proliferation upon migration to the dark zone. However, the mechanisms underlying how these GC-B cells reprogram mitochondrial bioenergetic functions to sustain cell division while overcoming hypoxia-driven energy stress are not understood. We found that microRNA (miR)-155 directly repressed the expression of hypoxia-induced histone lysine demethylase 2a, resulting in fine-tuning of histone H3 di-methylated lysine 36 levels. This optimized the expression of vital nuclear mitochondrial genes in LZ GC-B cells, thereby preventing excessive mitochondrial reactive oxygen species production and apoptosis. Thus, miR-155-regulated epigenetic mechanisms functions as a metabolic switch facilitating dynamic mitochondrial remodelling of LZ GC-B cells, ensuring positive selection and affinity maturation.