{"doi":"10.1093/jimmun/vkaf074","title":"B cell-expressed CD1d promotes MPL/TDCM lipid emulsion adjuvant effects in polysaccharide vaccines","abstract":"T cell-independent type 2 antigens (TI-2 Ags), such as pneumococcal polysaccharides, elicit weak immunoglobulin G (IgG) responses and are refractive to boosting. Overcoming this challenge is critical for improving vaccines. Previously, we demonstrated a lipid-based adjuvant composed of monophosphoryl lipid A, synthetic cord factor, and squalene significantly boosts primary and secondary IgM and IgG production against polysaccharide Ags. Herein, we show beta-2 microglobulin, but not MHC class II, is essential for adjuvant-induced increases in polysaccharide-specific IgG levels. Furthermore, we demonstrate CD1d expression is essential for optimal adjuvant-induced increases in IgG, but is not required for IgG responses to TI-2 Ags administered without adjuvant, with the exception of the bacterial cell wall polysaccharide component, phosphorylcholine. Adoptive transfer of splenic and peritoneal cells from VHB1-8 transgenic mice into CD1d-/- mice revealed adjuvant-induced increases in NP-Ficoll-specific IgG production by CD1d+/+ transgenic B cells, but not recipient B cells, suggesting B cell-expressed CD1d is critical for adjuvant-induced effects on TI-2 antibody responses. Consistent with this, bone marrow chimera mice with selective CD1d deficiency in B cells demonstrated B cell-expressed CD1d was dispensable for iNKT cell development and maintenance but was required for adjuvant-induced increases in protective levels of polysaccharide- and phosphorylcholine-specific IgG. Notably, both iNKT cells and CD1d crosslinking significantly increased IgG production by B cells coactivated with TI-2 Ag and adjuvant, suggesting iNKT-induced CD1d signaling may promote increased IgG production. In summary, our study reveals B cell-dependent CD1d expression is critical for effectiveness of a potent lipid-based adjuvant in augmenting polysaccharide- and phosphorylcholine-specific IgG responses.","journal":"The Journal of Immunology","year":2025,"id":552518,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":298291,"name":"Christina A. Daly","orcid":"0000-0001-7470-0454","position":1,"is_corresponding":false},{"id":832042,"name":"Andrew S. Bray","orcid":"0000-0001-6975-7122","position":2,"is_corresponding":false},{"id":515963,"name":"Allison M. Dyevoich","orcid":"0000-0002-4106-0435","position":3,"is_corresponding":false},{"id":831298,"name":"M. Ariel Spurrier","orcid":"0000-0002-3314-9683","position":4,"is_corresponding":false},{"id":474660,"name":"Karen M. Haas","orcid":"0000-0002-9951-1964","position":5,"is_corresponding":false},{"id":831744,"name":"Jamie Jennings‐Gee","orcid":null,"position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:54:33.203144Z","pmid":"40280183","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":[]}