{"doi":"10.1101/2021.09.10.459794","title":"Deletion of <i>Vhl</i> in <i>Dmp1</i> -expressing cells causes microenvironmental impairment of B cell lymphopoiesis","abstract":"ABSTRACT The contributions of skeletal cells to the processes of B cell development in the bone marrow (BM) have not been completely described. The von-Hippel Lindau protein (VHL) plays a key role in cellular responses to hypoxia. Previous work showed that Dmp1 -Cre; Vhl conditional knockout mice ( Vhl cKO), which delete Vhl in late osteoblasts and osteocytes, display dysregulated bone growth and reduction in B cells. Here, we investigated the mechanisms underlying the B cell defects using flow cytometry and high-resolution imaging. In the Vhl cKO BM, B cell progenitors were increased in frequency and number, whereas Hardy Fractions B-F were decreased. Vhl cKO Fractions B-C cells showed increased apoptosis and quiescence. Reciprocal BM chimeras confirmed a B cell-extrinsic source of the Vhl cKO B cell defects. In support of this, Vhl cKO BM serum contained reduced CXCL12 and elevated EPO levels. Staining of Vhl cKO B cells with an intracellular hypoxic marker indicated the natural existence of distinct B cell microenvironments that differ in local oxygen tensions. Additionally, intravital and ex vivo imaging revealed Vhl cKO BM blood vessels with increased diameter, frequency, volume, and a diminished blood-BM barrier. Our studies identify novel mechanisms linking altered bone homeostasis with drastic BM microenvironmental changes that dysregulate B cell development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221707,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":822902,"name":"Nastaran Abbasizadeh","orcid":null,"position":1,"is_corresponding":false},{"id":760978,"name":"Christian Burns","orcid":"0000-0003-2090-0252","position":2,"is_corresponding":false},{"id":822903,"name":"Hanna Taglinao","orcid":null,"position":3,"is_corresponding":false},{"id":686169,"name":"Joel A. Spencer","orcid":"0000-0002-4013-8763","position":4,"is_corresponding":false},{"id":422333,"name":"Jennifer O. Manilay","orcid":"0000-0002-1431-5295","position":5,"is_corresponding":false},{"id":572155,"name":"Betsabel Chicana","orcid":"0000-0001-7029-3476","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-18T23:53:59.302331Z","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":[]}