{"doi":"10.1126/sciimmunol.abn1250","title":"Atypical B cells up-regulate costimulatory molecules during malaria and secrete antibodies with T follicular helper cell support","abstract":"Several infectious and autoimmune diseases are associated with an expansion of CD21 − CD27 − atypical B cells (atBCs) that up-regulate inhibitory receptors and exhibit altered B cell receptor (BCR) signaling. The function of atBCs remains unclear, and few studies have investigated the biology of pathogen-specific atBCs during acute infection. Here, we performed longitudinal flow cytometry analyses and RNA sequencing of Plasmodium falciparum ( Pf )–specific B cells isolated from study participants before and shortly after febrile malaria, with simultaneous analysis of influenza hemagglutinin (HA)–specific B cells as a comparator. At the healthy baseline before the malaria season, individuals had similar frequencies of Pf - and HA-specific atBCs that did not differ proportionally from atBCs within the total B cell population. BCR sequencing identified clonal relationships between Pf -specific atBCs, activated B cells (actBCs), and classical memory B cells (MBCs) and revealed comparable degrees of somatic hypermutation. At the healthy baseline, Pf -specific atBCs were transcriptionally distinct from Pf -specific actBCs and classical MBCs. In response to acute febrile malaria, Pf -specific atBCs and actBCs up-regulated similar intracellular signaling cascades. Pf -specific atBCs showed activation of pathways involved in differentiation into antibody-secreting cells and up-regulation of molecules that mediate B-T cell interactions, suggesting that atBCs respond to T follicular helper (T FH ) cells. In the presence of T FH cells and staphylococcal enterotoxin B, atBCs of malaria-exposed individuals differentiated into CD38 + antibody-secreting cells in vitro, suggesting that atBCs may actively contribute to humoral immunity to infectious pathogens.","journal":"Science Immunology","year":2022,"id":246004,"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":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260432,"name":"Jeff Skinner","orcid":"0000-0001-5697-0442","position":1,"is_corresponding":false},{"id":108655,"name":"Sarah L. Anzick","orcid":"0000-0002-4907-513X","position":2,"is_corresponding":false},{"id":108298,"name":"Christopher M. Tipton","orcid":"0000-0002-5049-2571","position":3,"is_corresponding":false},{"id":629977,"name":"Mary Peterson","orcid":"0000-0001-6848-8709","position":4,"is_corresponding":false},{"id":260428,"name":"Shanping Li","orcid":"0000-0003-0998-2082","position":5,"is_corresponding":false},{"id":260425,"name":"Safiatou Doumbo","orcid":"0000-0002-0974-0860","position":6,"is_corresponding":false},{"id":260440,"name":"Kassoum Kayentao","orcid":"0000-0001-6877-0093","position":7,"is_corresponding":false},{"id":260441,"name":"Aïssata Ongoïba","orcid":"0000-0002-8797-497X","position":8,"is_corresponding":false},{"id":108657,"name":"Craig Martens","orcid":"0000-0001-8112-2234","position":9,"is_corresponding":false},{"id":260446,"name":"Boubacar Traoré","orcid":"0000-0001-5218-5981","position":10,"is_corresponding":false},{"id":260447,"name":"Peter D. Crompton","orcid":"0000-0001-5629-0412","position":11,"is_corresponding":false},{"id":260426,"name":"Christine S. Hopp","orcid":"0000-0002-0528-9531","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T00:23:43.438539Z","pmid":"35559666","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":[]}