{"doi":"10.1155/2013/807240","title":"Internalization of B Cell Receptors in Human EU12<i>μ</i>HC<sup>+</sup>Immature B Cells Specifically Alters Downstream Signaling Events","abstract":"<jats:p>It has been recognized for a long time that engagement of B cell antigen receptors (BCRs) on immature B cells or mature B cells leads to completely opposite cell fate decisions. The underlying mechanism remains unclear. Here, we show that crosslinking of BCRs on human EU12<jats:italic>μ</jats:italic>HC<jats:sup>+</jats:sup>immature B cells resulted in complete internalization of cell surface BCRs. After loss of cell surface BCRs, restimulation of EU12<jats:italic>μ</jats:italic>HC<jats:sup>+</jats:sup>cells showed impaired Ca<jats:sup>2+</jats:sup>flux, delayed SYK phosphorylation, and decreased CD19 and FOXO1 phosphorylation, which differ from those in mature Daudi or Ramos B cells with partial internalization of BCRs. In contrast, sustained phosphorylation and reactivation of ERK upon restimulation were observed in the EU12<jats:italic>μ</jats:italic>HC<jats:sup>+</jats:sup>cells after BCR internalization. Taken together, these results show that complete internalization of cell surface BCRs in EU12<jats:italic>μ</jats:italic>HC<jats:sup>+</jats:sup>cells specifically alters the downstream signaling events, which may favor receptor editing versus cell activation.</jats:p>","journal":"BioMed Research International","year":2013,"id":630398,"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":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1633122,"name":"Wanqin Xie","orcid":"0000-0003-0853-8633","position":1,"is_corresponding":false},{"id":1633123,"name":"Miles D. Lange","orcid":null,"position":2,"is_corresponding":false},{"id":1633124,"name":"Sang Yong Hong","orcid":"0000-0003-0877-461X","position":3,"is_corresponding":false},{"id":316074,"name":"Kaihong Su","orcid":null,"position":4,"is_corresponding":false},{"id":1452896,"name":"Zhixin Zhang","orcid":"0000-0003-1321-5273","position":5,"is_corresponding":false},{"id":756065,"name":"Jing Liu","orcid":"0000-0002-3588-2969","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Internalization of B Cell Receptors in Human EU12<i>μ</i>HC<sup>+</sup>Immature B Cells Specifically Alters Downstream Signaling Events","abstract":"<jats:p>It has been recognized for a long time that engagement of B cell antigen receptors (BCRs) on immature B cells or mature B cells leads to completely opposite cell fate decisions. The underlying mechanism remains unclear. Here, we show that crosslinking of BCRs on human EU12<jats:italic>μ</jats:italic>HC<jats:sup>+</jats:sup>immature B cells resulted in complete internalization of cell surface BCRs. After loss of cell surface BCRs, restimulation of EU12<jats:italic>μ</jats:italic>HC<jats:sup>+</jats:sup>cells showed impaired Ca<jats:sup>2+</jats:sup>flux, delayed SYK phosphorylation, and decreased CD19 and FOXO1 phosphorylation, which differ from those in mature Daudi or Ramos B cells with partial internalization of BCRs. In contrast, sustained phosphorylation and reactivation of ERK upon restimulation were observed in the EU12<jats:italic>μ</jats:italic>HC<jats:sup>+</jats:sup>cells after BCR internalization. Taken together, these results show that complete internalization of cell surface BCRs in EU12<jats:italic>μ</jats:italic>HC<jats:sup>+</jats:sup>cells specifically alters the downstream signaling events, which may favor receptor editing versus cell activation.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24222917","pmcid":"PMC3809603","openalex_id":null,"authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"AI074948","title":null},{"funder_name":"National Institutes of Health","grant_id":"AI076475","title":null},{"funder_name":"National Institutes of Health","grant_id":"AI073174","title":null},{"funder_name":"National Institutes of Health","grant_id":"AR059351","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI073174","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI074948","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R01 AR059351","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI076475","title":null}],"total_grants":8,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://downloads.hindawi.com/journals/bmri/2013/807240.pdf","host_type":"publisher"},{"url":"http://downloads.hindawi.com/journals/bmri/2013/807240.pdf","host_type":"publisher"},{"url":"http://downloads.hindawi.com/journals/bmri/2013/807240.xml","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3809603","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC3809603","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC3809603?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":["B-Lymphocytes","Humans","Intracellular Signaling Peptides and Proteins","Receptors, Antigen, B-Cell","Antigens, CD19","Signal Transduction","Cell Differentiation","Phosphorylation","Surface Properties","Forkhead Transcription Factors","Protein-Tyrosine Kinases","Syk Kinase","Forkhead Box Protein O1"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T21:11:37.012738Z","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":[]}