{"doi":"10.1101/2021.06.10.447979","title":"PD-1 checkpoint blockade disrupts CD4 T cell regulated adaptive B cell tolerance to foreign antigens","abstract":"SUMMARY Adaptive B cell immunity to environmental antigens must be regulated by multiple CD4 T cell dependent tolerance mechanisms. Using integrated single cell strategies, we demonstrate that acute PD-1 blockade induces extensive and selective local anti-inflammatory IgG1 plasma cell (PC) differentiation. Expansion of pre-existing IgG1 germinal center (GC) B cell and enhanced GC programming without memory B cell involvement reveals an isotype-specific GC checkpoint that blocks steady-state IgG1 antibody maturation. While there was no adjuvant impact on immunization, acute PD-1 checkpoint blockade exaggerates anti-commensal IgG1 antibody production, alters microbiome composition and exerts its action in a CD4 T cell dependent manner. These findings reveal a PD-1 controlled adaptive B cell tolerance checkpoint that selectively constrains maturation of pre-existing anti-inflammatory antibodies to prevent over-reaction to steady-state foreign antigens. In Brief PD-1 controls an adaptive B cell tolerance checkpoint in steady-state germinal centers to inhibit the maturation and production of IgG1 antibody with pre-existing foreign specificities. Highlights – Acute PD-1 blockade induces extensive IgG1 PC differentiation at homeostasis – PD-1 blockade releases an IgG1 GC B cell checkpoint that drives expansion and PC formation – No adjuvant effect on foreign antigen but expansion of pre-existing IgG1 specificities to non-self – PD-1 exerts CD4 T cell dependent tolerance in the GC to restrict IgG1 maturation to non-self Graphical Abstract","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215115,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"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":781412,"name":"Andrew G. Shuparski","orcid":"0000-0002-3703-0890","position":1,"is_corresponding":false},{"id":809348,"name":"Brett Higgins","orcid":"0000-0003-2006-6704","position":2,"is_corresponding":false},{"id":781418,"name":"Louise J. McHeyzer‐Williams","orcid":"0000-0002-8860-2983","position":3,"is_corresponding":false},{"id":781419,"name":"Michael G. McHeyzer‐Williams","orcid":"0000-0003-0459-569X","position":4,"is_corresponding":false},{"id":781415,"name":"Chad Dufaud","orcid":"0000-0002-7273-3540","position":0,"is_corresponding":true}],"reference_count":100,"raw_metadata":null,"created_at":"2026-07-18T23:52:51.201033Z","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":[]}