{"doi":"10.4049/jimmunol.168.9.4344","title":"Transmodulation of BCR Signaling by Transduction- Incompetent Antigen Receptors: Implications for Impaired Signaling in Anergic B Cells","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>B cell tolerance can be maintained by functional inactivation, or anergy, wherein B cell Ag receptors (BCR) remain capable of binding Ag, but are unable to transduce signals. Although the molecular mechanisms underlying this unresponsiveness are unknown, some models of B cell anergy are characterized by disruption of proximal BCR signaling events, and by destabilization of the BCR complex. Receptor destabilization is manifest by a reduced ability to coimmunoprecipitate membrane Ig with the Ig-α/Ig-β signal-transducing complex. To begin to explore the possibility that anergy is the consequence of receptor destabilization, we analyzed a panel of B lymphoma transfectants expressing constant amounts of signal-competent Ag receptors and varied amounts of a receptor with identical specificity, but bearing mutations that render it incapable of interacting with Ig-α/Ig-β. This analysis revealed that coaggregation of signal-incompetent receptors prevented Ag-induced Ig-α and Syk phosphorylation, mobilization of Ca2+, and the up-regulation of CD69 mediated by competent receptors. In contrast, Ag-induced Cbl and Erk phosphorylation were unaffected. Data indicate that coaggregation of destabilized receptors (as few as ∼15% of total) with signal-competent receptors significantly affects the ability of competent receptors to transduce signals. Thus, BCR destabilization may underlie the Ag unresponsiveness of anergic B cells.</jats:p>","journal":"The Journal of Immunology","year":2002,"id":632613,"datarank":0.5570358100056463,"base_score":3.713572066704308,"endowment":3.713572066704308,"self_citation_contribution":0.5570358100056463,"citation_network_contribution":0.0,"self_endowment_contribution":0.5570358100056463,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"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":1639872,"name":"Kathy M Burke","orcid":null,"position":1,"is_corresponding":false},{"id":1639873,"name":"Michelle Sleater","orcid":null,"position":2,"is_corresponding":false},{"id":1639874,"name":"John C Cambier","orcid":null,"position":3,"is_corresponding":false},{"id":1639871,"name":"Barbara J Vilen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Transmodulation of BCR Signaling by Transduction- Incompetent Antigen Receptors: Implications for Impaired Signaling in Anergic B Cells","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>B cell tolerance can be maintained by functional inactivation, or anergy, wherein B cell Ag receptors (BCR) remain capable of binding Ag, but are unable to transduce signals. Although the molecular mechanisms underlying this unresponsiveness are unknown, some models of B cell anergy are characterized by disruption of proximal BCR signaling events, and by destabilization of the BCR complex. Receptor destabilization is manifest by a reduced ability to coimmunoprecipitate membrane Ig with the Ig-α/Ig-β signal-transducing complex. To begin to explore the possibility that anergy is the consequence of receptor destabilization, we analyzed a panel of B lymphoma transfectants expressing constant amounts of signal-competent Ag receptors and varied amounts of a receptor with identical specificity, but bearing mutations that render it incapable of interacting with Ig-α/Ig-β. This analysis revealed that coaggregation of signal-incompetent receptors prevented Ag-induced Ig-α and Syk phosphorylation, mobilization of Ca2+, and the up-regulation of CD69 mediated by competent receptors. In contrast, Ag-induced Cbl and Erk phosphorylation were unaffected. Data indicate that coaggregation of destabilized receptors (as few as ∼15% of total) with signal-competent receptors significantly affects the ability of competent receptors to transduce signals. Thus, BCR destabilization may underlie the Ag unresponsiveness of anergic B cells.</jats:p>","is_dataset_classified":null,"base_score":3.713572066704308,"endowment":3.713572066704308,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11970976","pmcid":"PMC3726184","openalex_id":"https://openalex.org/W1513383992","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"K22 AI001756","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"P01 AI022295","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI22295","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG013983","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI26519","title":null},{"funder_name":"NIA NIH HHS","grant_id":"AG13983","title":null}],"total_grants":6,"fwci":3.4581,"citation_percentile":0.91632343,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2014,"count":2},{"year":2017,"count":1},{"year":2018,"count":1},{"year":2019,"count":3},{"year":2020,"count":1}],"oa_status":"bronze","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://journals.aai.org/jimmunol/article-pdf/168/9/4344/1150575/4344.pdf","host_type":"journal"},{"url":"https://journals.aai.org/jimmunol/article-pdf/168/9/4344/1150575/4344.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jimmunol/article-pdf/168/9/4344/62551687/4344.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.168.9.4344","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11970976","host_type":"repository"},{"url":"http://europepmc.org/articles/PMC3726184","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3726184","host_type":"repository"}],"fields_of_study":["Parasitic Infections and Diagnostics","T-cell and B-cell Immunology","Cytomegalovirus and herpesvirus research"],"mesh_terms":["Syk Kinase","CD69 Antigens","Animals","Antigens","Antigens, Differentiation, T-Lymphocyte","B-Lymphocytes","Calcium","Cells, Cultured","Enzyme Precursors","Immunoglobulin D","Immunoglobulin M","Phosphorylation","Protein-Tyrosine Kinases","Proto-Oncogene Proteins","Receptor Aggregation","Receptors, Antigen, B-Cell","Tumor Cells, Cultured","Signal Transduction","Antigens, CD","Lymphoma, B-Cell","Clonal Anergy","Mitogen-Activated Protein Kinases","Lectins, C-Type","Ubiquitin-Protein Ligases","Intracellular Signaling Peptides and Proteins","Proto-Oncogene Proteins c-cbl","CD79 Antigens"],"keywords":["Signal transduction","Receptor","breakpoint cluster region","Cell biology","Transduction (biophysics)","Biology","Immunology","Genetics","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T10:03:54.153204Z","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":[]}