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These cells are found in large numbers in the gut lamina propria and the bone marrow (BM). In this study, we found that IgA+ PCs in the gut secrete significantly fewer antibodies on a per-cell basis compared to BM PCs in B6 mice. While the cell-intrinsic and -extrinsic signals responsible for regulating BM PC function have been extensively studied, these regulatory signals are understudied in gut PCs. Recent studies have established that metabolism is a critical component to optimized PC function in the BM. To evaluate the metabolic pathways utilized by tissue-resident IgA+ PCs, we utilized the flow cytometry\u2013based SCENITH assay and determined that gut IgA+ PCs have increased glycolytic capacity, in contrast to increased mitochondrial dependency in BM IgA+ PCs. Consistent with a glycolytic phenotype, gut IgA+ PCs have a high capacity to uptake glucose, high mTORC1 activity, and low cellular reactive oxygen species. To determine if glycolysis is restricting gut IgA+ PCs\u2019 antibody secretion, we used inhibitors to target key bioenergetic pathways. We found that antibody secretion is enhanced by inhibiting the switch to glycolysis, and conversely restricted when PCs are prevented from utilizing oxidative phosphorylation. Herein, we identified that tissue-specific metabolic programs regulate PC function, where glycolysis restricts antibody secretion in the gut. Understanding how function is regulated in tissue-resident PCs can be leveraged to optimize better antibody responses for maintaining intestinal homeostasis, targeting mucosal pathogens, and optimizing mucosal vaccines.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf310","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T23:52:43Z","timestamp":1764805963000},"source":"Crossref","is-referenced-by-count":4,"title":["Restriction of IgA secretion in gut plasma cells is driven by a tissue-specific glycolytic program"],"prefix":"10.1093","volume":"215","author":[{"given":"Victoria","family":"Zoccoli-Rodriguez","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, State University of New York Upstate Medical University , Syracuse, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Iwaniec","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, State University of New York Upstate Medical University , Syracuse, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2797-5604","authenticated-orcid":false,"given":"Joel R","family":"Wilmore","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, State University of New York Upstate Medical University , Syracuse, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"2026052212165211000_vkaf310-B1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.0105-2896.2005.00283.x","article-title":"Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties","volume":"206","author":"Brandtzaeg","year":"2005","journal-title":"Immunol 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