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Metabolic processes and products regulate aspects of B cell proliferation and differentiation into germinal center (GC) and PC states along with Ab diversification. However, there is little information about lymphoid-cell-intrinsic functions of enzymes that mediate ether lipid biosynthesis. Imaging mass spectrometry (IMS) results had indicated that concentrations of a number of these phospholipids were substantially enhanced in GC compared to the background average in spleens, but it was unclear if biosynthesis in B cells was a basis for this finding, or whether cell-intrinsic biosynthesis contributes to B cell physiology or Ab responses. Ether lipid biosynthesis can involve the enzyme PexRAP, encoded by the\n                    <jats:italic>Dhrs7b<\/jats:italic>\n                    gene. Using IMS and immunization experiments in mouse models with inducible\n                    <jats:italic>Dhrs7b<\/jats:italic>\n                    loss of function, we now show that B-lineage-intrinsic expression of PexRAP promotes the magnitude and affinity maturation of a serological response. Moreover, the data revealed a\n                    <jats:italic>Dhrs7b<\/jats:italic>\n                    -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.\n                  <\/jats:p>","DOI":"10.7554\/elife.104580","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T09:25:09Z","timestamp":1736933109000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.104580","source":"Crossref","is-referenced-by-count":0,"title":["B cell expression of an enzymatic intermediary in ether lipid biosynthesis promotes antibody responses and germinal center size"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6463-4032","authenticated-orcid":true,"given":"Sung Hoon","family":"Cho","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05dq2gs74","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology-Microbiology-Immunology, Vanderbilt University Medical Center","place":["Nashville, United 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