Epigenetic and metabolic reprogramming support plasma cell differentiation in germinal centers

The germinal center (GC) is a specialized structure that ensures the production of high-quality antibodies. Although recent studies have pinpointed the existence of a pre-plasma cell (prePC) population within mouse GC B cells, it remains unclear how these prePCs mechanistically differentiate into PCs. Additionally, there is a lack of validation of these findings in human cells. Here, we demonstrate CD205 is highly expressed in prePCs both in mouse and in human. The histone H3 lysine 27 demethylase Kdm6b, not Kdm6a, potently enhances the differentiation of prePCs into bona fide PCs by removing repressive H3K27me3 marks at the Irf4 locus. Interestingly, prePCs favor glutamine metabolism, which provides α-ketoglutarate as a substrate for the demethylation reaction of Kdm6b. Thus, prePCs require metabolic and epigenetic reprogramming to differentiate into PCs in the GC.