{"doi":"10.4049/jimmunol.2200053","title":"TNF-α Limits Serological Memory by Disrupting the Bone Marrow Niche","abstract":"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. PC motility and egress in the BM are triggered within 6 h of recombinant TNF-α treatment. In addition to promoting egress, TNF-α signaling also prevented re-engraftment into the BM, leading to reduced PC survival. Although other inflammatory stimuli can promote PC egress, TNF-α signaling is necessary for limiting the PC capacity in the BM. Collectively, these data characterize how TNF-α-mediated inflammation attenuates the durability of serological memory and shapes the overall size and composition of the Ab-secreting cell pool in the BM.","journal":"The Journal of Immunology","year":2023,"id":353557,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":109542,"name":"Ethan Laudermilch","orcid":"0000-0001-7488-1718","position":1,"is_corresponding":false},{"id":505997,"name":"Zachary Benet","orcid":"0000-0002-8679-7545","position":2,"is_corresponding":false},{"id":1025560,"name":"Luis Ovando","orcid":"0000-0002-6449-7365","position":3,"is_corresponding":false},{"id":109548,"name":"Kartik Chandran","orcid":"0000-0003-0232-7077","position":4,"is_corresponding":false},{"id":310628,"name":"David Fooksman","orcid":"0000-0001-7601-4255","position":5,"is_corresponding":false},{"id":1100252,"name":"Tonya Aaron","orcid":"0000-0001-5419-3213","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T01:13:02.680107Z","pmid":"36645344","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}