{"doi":"10.4049/jimmunol.169.5.2292","title":"Expression of CD28 by Bone Marrow Stromal Cells and Its Involvement in B Lymphopoiesis","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Young mice lacking CD28 have normal numbers of peripheral B cells; however, abnormalities exist in the humoral immune response that may result from an intrinsic defect in the B cells. The goal of this study was to assess whether CD28 could be involved in the development of B cells. CD28 mRNA was detected preferentially in the fraction of bone marrow enriched for stromal cells. Flow cytometry and RT-PCR analysis demonstrated that CD28 was also expressed by primary-cultured stromal cells that supported B lymphopoiesis. Confocal microscopy revealed that in the presence of B-lineage cells, CD28 was localized at the contact interface between B cell precursors and stromal cells. In addition, CD80 was detected on 2–6% of freshly isolated pro- and pre-B cells, and IL-7 stimulation led to induction of CD86 on 15–20% of pro- and pre-B cells. We also observed that stromal cell-dependent production of B-lineage cells in vitro was greater on stromal cells that lacked CD28. Finally, the frequencies of B-lineage precursors in the marrow from young (4- to 8-wk-old) CD28−/− mice were similar to those in wild-type mice; however, older CD28−/− mice (15–19 mo old) exhibited a 30% decrease in pro-B cells and a 50% decrease in pre-B cells vs age-matched controls. Our results suggest that CD28 on bone marrow stromal cells participates in stromal-dependent regulation of B-lineage cells in the bone marrow. The localization of CD28 at the stromal cell:B cell precursor interface suggests that molecules important for T cell:B cell interactions in the periphery may also participate in stromal cell:B cell precursor interactions in the bone marrow.</jats:p>","journal":"The Journal of Immunology","year":2002,"id":598458,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"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":1533558,"name":"Robert P Stephan","orcid":null,"position":1,"is_corresponding":false},{"id":1533559,"name":"Ron-Gran Apilado","orcid":null,"position":2,"is_corresponding":false},{"id":1533560,"name":"Deborah A Lill-Elghanian","orcid":null,"position":3,"is_corresponding":false},{"id":1533561,"name":"Kelvin P Lee","orcid":null,"position":4,"is_corresponding":false},{"id":355366,"name":"Bhaskar Saha","orcid":"0000-0002-5833-7912","position":5,"is_corresponding":false},{"id":1533562,"name":"Pamela L Witte","orcid":null,"position":6,"is_corresponding":false},{"id":1533557,"name":"Kirstin Gray Parkin","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Expression of CD28 by Bone Marrow Stromal Cells and Its Involvement in B Lymphopoiesis","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Young mice lacking CD28 have normal numbers of peripheral B cells; however, abnormalities exist in the humoral immune response that may result from an intrinsic defect in the B cells. The goal of this study was to assess whether CD28 could be involved in the development of B cells. CD28 mRNA was detected preferentially in the fraction of bone marrow enriched for stromal cells. Flow cytometry and RT-PCR analysis demonstrated that CD28 was also expressed by primary-cultured stromal cells that supported B lymphopoiesis. Confocal microscopy revealed that in the presence of B-lineage cells, CD28 was localized at the contact interface between B cell precursors and stromal cells. In addition, CD80 was detected on 2–6% of freshly isolated pro- and pre-B cells, and IL-7 stimulation led to induction of CD86 on 15–20% of pro- and pre-B cells. We also observed that stromal cell-dependent production of B-lineage cells in vitro was greater on stromal cells that lacked CD28. Finally, the frequencies of B-lineage precursors in the marrow from young (4- to 8-wk-old) CD28−/− mice were similar to those in wild-type mice; however, older CD28−/− mice (15–19 mo old) exhibited a 30% decrease in pro-B cells and a 50% decrease in pre-B cells vs age-matched controls. Our results suggest that CD28 on bone marrow stromal cells participates in stromal-dependent regulation of B-lineage cells in the bone marrow. The localization of CD28 at the stromal cell:B cell precursor interface suggests that molecules important for T cell:B cell interactions in the periphery may also participate in stromal cell:B cell precursor interactions in the bone marrow.</jats:p>","is_dataset_classified":null,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12193694","pmcid":null,"openalex_id":"https://openalex.org/W1939497685","authors":[],"funders":[{"funder_name":"NIA NIH HHS","grant_id":"K07AG00997","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG013874","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01AG13874","title":null},{"funder_name":"NIA NIH HHS","grant_id":"K07 AG000997","title":null}],"total_grants":4,"fwci":0.1804,"citation_percentile":0.45588798,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":3},{"year":2016,"count":2},{"year":2017,"count":1},{"year":2018,"count":1},{"year":2019,"count":1},{"year":2024,"count":3}],"oa_status":"closed","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/jimmunol/article-pdf/169/5/2292/62557135/2292.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.169.5.2292","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12193694","host_type":"repository"}],"fields_of_study":["T-cell and B-cell Immunology","Immunotherapy and Immune Responses","Immune Response and Inflammation","Aging","Animals","B-Lymphocyte Subsets","Bone Marrow Cells","CD28 Antigens","Cell Communication","Cell Differentiation","Cell Division","Cell Line","Cell Lineage","Cell Survival","Cells, Cultured","Female","Ligands","Mice","Mice, Inbred BALB C","Mice, Inbred C57BL","Mice, Knockout","Stem Cells","Stromal Cells","T-Lymphocyte Subsets"],"mesh_terms":["Aging","Animals","Bone Marrow Cells","Cell Communication","Cell Differentiation","Cell Division","Cell Line","Cell Survival","Cells, Cultured","Female","Ligands","Mice, Inbred BALB C","Mice, Inbred C57BL","Stem Cells","B-Lymphocyte Subsets","T-Lymphocyte Subsets","Stromal Cells","CD28 Antigens","Mice, Knockout","Cell Lineage","Mice"],"keywords":["Stromal cell","Lymph node stromal cell","Lymphopoiesis","CD28","Bone marrow","Haematopoiesis","Biology","B cell","CD80","T cell","CD86","CD40","Molecular biology","CD19","Flow cytometry","Cell biology","Immune system","Immunology","Chemistry","Stem cell","Cancer research","Cytotoxic T cell","In vitro","Antibody","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T15:45:40.671889Z","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":[]}