The peroxisomal lipid-synthesizing enzyme, PexRAP promotes antibody responses and germinal center size 4825

Description Metabolic reprogramming and intermediary metabolism play pivotal roles in B cell survival, proliferation, differentiation into germinal center (GC) and plasma cell as well as Ab diversification. However, there is little information about lymphoid cell-intrinsic functions of enzymes that mediate lipid biosynthesis. Previously, using imaging mass spectrometry (IMS), we observed that concentrations of many phospholipids were substantially enhanced in GC compared to the outside of GC. However, it was not clear whether the cell-intrinsic lipid biosynthesis contributes to B cell physiology or Ab responses. Peroxisomal enzyme PexRAP mediates the synthesis of ether phospholipids. Using combinations of IMS and mouse models with inducible PexRAP loss-of-function, we show that B lineage-intrinsic expression of PexRAP promotes the magnitude of Ag-specific Ab response. Moreover, the data revealed a PexRAP-dependent increase in ether phospholipids in primary follicles with a more prominent increase in GC. Mechanistically, PexRAP impacted B cell proliferation via enhanced survival associated with controlling levels of ROS and membrane peroxidation. These findings reveal a vital role of this peroxisomal enzyme in B cell homeostasis and the physiology of humoral immunity.