{"doi":"10.1101/2025.04.21.649586","title":"Secondary lymphoid organ stroma activate and elaborate regulatory T cells to suppress autoantibody production in a novel model of systemic autoimmunity","abstract":"ABSTRACT Preclinical models of lupus indicate that T cell-B cell collaboration drives pathogenic antinuclear antibody (ANA) production and sustains T cell activation. Mechanisms that normally limit T cell activation of autoreactive B cells remain incompletely resolved but potentially include the absence of autoreactive effector T cell subsets and/or the presence of autoantigen-specific regulatory T cells (Tregs). Several studies have addressed this issue by using experimental systems dependent on transgenic autoreactive B cells, but much less is known about the activation of autoreactive B cells present in a polyclonal repertoire. We have now explored the role of effector T cells and Tregs using mice that express an inducible pseudo-autoantigen on antigen presenting cells (APCs) including a normal B cell repertoire. Bone marrow chimera experiments demonstrated that radioresistant non-hematopoietic stromal APCs (rAPC) present in the thymus and in peripheral lymphoid tissue induced the differentiation and expansion of a subset of CD62L + CD69 + Tregs associated with decreased autoantibody production and MHC-II. In this study, we show that secondary lymph node stromal cells may be crucial for suppression of endogenous autoreactive B cells in the setting of robust T cell help.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":565018,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":533236,"name":"Ann Marshak‐Rothstein","orcid":"0000-0003-2136-8130","position":1,"is_corresponding":false},{"id":908116,"name":"Tia Y. Brodeur","orcid":"0000-0001-6845-9350","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:56:24.872312Z","pmid":null,"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":[]}