{"doi":"10.4049/jimmunol.173.4.2245","title":"TNF Family Member B Cell-Activating Factor (BAFF) Receptor-Dependent and -Independent Roles for BAFF in B Cell Physiology","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>The cytokine TNF family member B cell-activating factor (BAFF; also termed BLyS) is essential for B cell generation and maintenance. Three receptors have been identified that bind to BAFF: transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI); B cell maturation Ag (BCMA); and BAFF-R. Recently, it was shown that A/WySnJ mice, which contain a dramatically reduced peripheral B cell compartment due to decreased B cell life span, express a mutant BAFF-R. This finding, together with normal or enhanced B cell generation in mice deficient for BCMA or TACI, respectively, suggested that the interaction of BAFF with BAFF-R triggers signals essential for the generation and maintenance of mature B cells. However, B cells in mice deficient for BAFF differ phenotypically and functionally from A/WySnJ B cells. Residual signaling through the mutant BAFF-R could account for these differences. Alternatively, dominant-negative interference by the mutant receptor could lead to an overestimation of the importance of BAFF-R. To resolve this issue, we generated BAFF-R-null mice. Baff-r−/− mice display strongly reduced late transitional and follicular B cell numbers and are essentially devoid of marginal zone B cells. Overexpression of Bcl-2 rescues mature B cell development in Baff-r−/− mice, suggesting that BAFF-R mediates a survival signal. CD21 and CD23 surface expression are reduced on mature Baff-r−/− B cells, but not to the same extent as on mature B cells in BAFF-deficient mice. In addition, we found that Baff-r−/− mice mount significant, but reduced, Ag-specific Ab responses and are able to form spontaneous germinal centers in mesenteric lymph nodes. The reduction in Ab titers correlates with the reduced B cell numbers in the mutant mice.</jats:p>","journal":"The Journal of Immunology","year":2004,"id":622152,"datarank":0.885395000010205,"base_score":5.902633333401366,"endowment":5.902633333401366,"self_citation_contribution":0.885395000010205,"citation_network_contribution":0.0,"self_endowment_contribution":0.885395000010205,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":365,"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":1335483,"name":"Stefano Casola","orcid":"0000-0001-5580-0986","position":1,"is_corresponding":false},{"id":1606895,"name":"Jeffery L Kutok","orcid":null,"position":2,"is_corresponding":false},{"id":1606897,"name":"Klaus Rajewsky","orcid":null,"position":3,"is_corresponding":false},{"id":1606899,"name":"Marc Schmidt-Supprian","orcid":null,"position":4,"is_corresponding":false},{"id":1606893,"name":"Yoshiteru Sasaki","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"TNF Family Member B Cell-Activating Factor (BAFF) Receptor-Dependent and -Independent Roles for BAFF in B Cell Physiology","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>The cytokine TNF family member B cell-activating factor (BAFF; also termed BLyS) is essential for B cell generation and maintenance. Three receptors have been identified that bind to BAFF: transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI); B cell maturation Ag (BCMA); and BAFF-R. Recently, it was shown that A/WySnJ mice, which contain a dramatically reduced peripheral B cell compartment due to decreased B cell life span, express a mutant BAFF-R. This finding, together with normal or enhanced B cell generation in mice deficient for BCMA or TACI, respectively, suggested that the interaction of BAFF with BAFF-R triggers signals essential for the generation and maintenance of mature B cells. However, B cells in mice deficient for BAFF differ phenotypically and functionally from A/WySnJ B cells. Residual signaling through the mutant BAFF-R could account for these differences. Alternatively, dominant-negative interference by the mutant receptor could lead to an overestimation of the importance of BAFF-R. To resolve this issue, we generated BAFF-R-null mice. Baff-r−/− mice display strongly reduced late transitional and follicular B cell numbers and are essentially devoid of marginal zone B cells. Overexpression of Bcl-2 rescues mature B cell development in Baff-r−/− mice, suggesting that BAFF-R mediates a survival signal. CD21 and CD23 surface expression are reduced on mature Baff-r−/− B cells, but not to the same extent as on mature B cells in BAFF-deficient mice. In addition, we found that Baff-r−/− mice mount significant, but reduced, Ag-specific Ab responses and are able to form spontaneous germinal centers in mesenteric lymph nodes. The reduction in Ab titers correlates with the reduced B cell numbers in the mutant mice.</jats:p>","is_dataset_classified":null,"base_score":5.902633333401366,"endowment":5.902633333401366,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15294936","pmcid":null,"openalex_id":"https://openalex.org/W2159917672","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"1R37AI054636","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI057947","title":null}],"total_grants":2,"fwci":5.7804,"citation_percentile":0.97122823,"influential_citations":0,"citation_trend":[{"year":2012,"count":12},{"year":2013,"count":27},{"year":2014,"count":15},{"year":2015,"count":21},{"year":2016,"count":17},{"year":2017,"count":16},{"year":2018,"count":17},{"year":2019,"count":13},{"year":2020,"count":14},{"year":2021,"count":20},{"year":2022,"count":11},{"year":2023,"count":8},{"year":2024,"count":13},{"year":2025,"count":7},{"year":2026,"count":3}],"oa_status":"bronze","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://journals.aai.org/jimmunol/article-pdf/173/4/2245/1314496/2245.pdf","host_type":"journal"},{"url":"https://journals.aai.org/jimmunol/article-pdf/173/4/2245/1314496/2245.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jimmunol/article-pdf/173/4/2245/62604232/2245.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.173.4.2245","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15294936","host_type":"repository"},{"url":"https://hdl.handle.net/2434/1157827","host_type":"repository"}],"fields_of_study":["Immune Cell Function and Interaction","T-cell and B-cell Immunology","Immunotherapy and Immune Responses"],"mesh_terms":["Animals","Antibody Formation","B-Lymphocytes","Cell Differentiation","Flow Cytometry","Immune System","Immunoglobulins","Immunohistochemistry","Membrane Proteins","Tumor Necrosis Factor-alpha","Receptors, IgE","Receptors, Complement 3d","Germinal Center","Proto-Oncogene Proteins c-bcl-2","Reverse Transcriptase Polymerase Chain Reaction","Mice","B-Cell Activating Factor"],"keywords":["B-cell activating factor","Tumor necrosis factor alpha","Tumor necrosis factor receptor","Receptor","Cell biology","B cell","Cell","Biology","Immunology","Antibody","Genetics"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T18:24:14.602890Z","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":[]}