biostudies-literatureAaron TNIAID NIH HHSNHLBI NIH HHSAlbert Einstein Cancer CenterHHS | NIH | National Institute of Allergy and Infectious DiseasesHHS | NIH | National Heart, Lung, and Blood InstituteNCI NIH HHS595-608https://www.ebi.ac.uk/biostudies/studies/S-EPMC9998356biostudies-literatureUnknown210(5)Both infection and autoimmune disease can disrupt pre-existing Ab titers leading to diminished serological memory, yet the underlying mechanisms are not well understood. In this article, we report that TNF-α, an inflammatory cytokine, is a master regulator of the plasma cell (PC) niche in the bone marrow (BM). Acute rTNF-α treatment depletes previously existing Ab titers after vaccination by limiting PC occupancy or retention in the BM. Consistent with this phenomenon, mice lacking TNF-α signaling have elevated PC capacity in the BM and higher Ab titers. Using BM chimeric mice, we found that PC egress from the BM is regulated in a cell-extrinsic manner, by radiation-resistant cells via TNF-α receptor 1 signaling, leading to increased vascular permeability and CD138 downregulation on PCs. PJournal of immunology (Baltimore, Md. : 1950)TNF-α Limits Serological Memory by Disrupting the Bone Marrow Niche.PMC9998356R01 AI132633F32 HL149155P30 CA013330R01AI132633R01HL141491R01 HL141491P30CA013330R01 HL152637F32HL149155Aaron TOvando LJChandran KBenet ZFooksman DLaudermilch EfalseTNF-α Limits Serological Memory by Disrupting the Bone Marrow Niche.Both infection and autoimmune disease can disrupt pre-existing Ab titers leading to diminished serological memory, yet the underlying mechanisms are not well understood. In this article, we report that TNF-α, an inflammatory cytokine, is a master regulator of the plasma cell (PC) niche in the bone marrow (BM). Acute rTNF-α treatment depletes previously existing Ab titers after vaccination by limiting PC occupancy or retention in the BM. Consistent with this phenomenon, mice lacking TNF-α signaling have elevated PC capacity in the BM and higher Ab titers. Using BM chimeric mice, we found that PC egress from the BM is regulated in a cell-extrinsic manner, by radiation-resistant cells via TNF-α receptor 1 signaling, leading to increased vascular permeability and CD138 downregulation on PCs. P2023-01-01T00:00:00Z2023 Mar2025-04-03T23:49:51.443Z2025-04-03T23:49:51.443ZS-EPMC99983563664534410.4049/jimmunol.2200053