{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:05:54Z","timestamp":1791165954545,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>B cell A disintegrin and metalloproteinase 10 (ADAM10) is required for the development and maintenance of proper secondary lymphoid tissue architecture; however, the underlying mechanism remains unclear. In this study, we show disturbances in naive lymph node architecture from B cell\u2013specific ADAM10-deficient mice (ADAM10B\u2212\/\u2212) including loss of B lymphocyte\/T lymphocyte compartmentalization, attenuation of follicular dendritic cell reticula, excessive collagen deposition, and increased high endothelial venule formation. Because TNF-\u03b1 signaling is critical for secondary lymphoid tissue architecture, we examined compensatory changes in ADAM17 and TNF-\u03b1 in ADAM10B\u2212\/\u2212 B cells. Surprisingly, defective follicular development in these mice was associated with increased rather than decreased TNF-\u03b1 expression. In this article, we describe an increase in TNF-\u03b1 message, mRNA stability, soluble protein release, and membrane expression in ADAM10B\u2212\/\u2212 B cells compared with wild type (WT), which coincides with increased ADAM17 message and protein. To assess the mechanistic contribution of excessive TNF-\u03b1 to abnormal lymphoid architecture in ADAM10B\u2212\/\u2212 mice, we performed a bone marrow reconstitution study. Rectification of WT architecture was noted only in irradiated WT mice reconstituted with ADAM10B\u2212\/\u2212 + TNF knockout bone marrow because of normalization of TNF-\u03b1 levels not seen in ADAM10B\u2212\/\u2212 alone. We conclude that ADAM17 overcompensation causes excessive TNF-\u03b1 shedding and further upregulation of TNF-\u03b1 expression, creating an aberrant signaling environment within B cell cortical regions of ADAM10B\u2212\/\u2212 lymph nodes, highlighting a key interplay between B cell ADAM10 and ADAM17 with respect to TNF-\u03b1 homeostasis.<\/jats:p>","DOI":"10.4049\/jimmunol.1302042","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T05:42:58Z","timestamp":1384407778000},"page":"5951-5958","source":"Crossref","is-referenced-by-count":22,"title":["Disturbed Follicular Architecture in B Cell A Disintegrin and Metalloproteinase (ADAM)10 Knockouts Is Mediated by Compensatory Increases in ADAM17 and TNF-\u03b1 Shedding"],"prefix":"10.1093","volume":"191","author":[{"given":"Lauren","family":"Folgosa","sequence":"first","affiliation":[{"name":"Center for Clinical and Translational Research, Virginia Commonwealth University , Richmond, VA 23298"},{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University , Richmond, VA 23298"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah B","family":"Zellner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University , Richmond, VA 23298"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohey Eldin","family":"El Shikh","sequence":"additional","affiliation":[{"name":"Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University of London , Charterhouse Square campus, London EC1M 6BQ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H","family":"Conrad","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University , Richmond, VA 23298"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,12,15]]},"reference":[{"key":"2025032406051087600_r1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.mam.2008.08.001","article-title":"The ADAM metalloproteinases","volume":"29","author":"Edwards","year":"2008","journal-title":"Mol. 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