{"doi":"10.1101/2020.04.12.030049","title":"<i>Plasmodium falciparum</i> -specific IgM B cells dominate in children, expand with malaria and produce parasite inhibitory IgM","abstract":"Abstract IgG antibodies are known to play a central role in naturally acquired immunity to blood-stage malaria in humans, but little is known about the IgM response to blood-stage malaria, the mechanisms by which IgM may protect, or the underlying biology of Plasmodium falciparum ( Pf )-specific IgM B cells. In a Mali cohort spanning infants to adults we conducted a longitudinal analysis of B cells specific for the Pf blood-stage antigens AMA1 and MSP1, as well as the comparator antigen influenza hemagglutinin (HA). At the uninfected baseline, before the malaria season, Pf -specific memory B cells (MBCs) in children are disproportionally IgM + and only gradually shift to IgG + with age, in contrast to HA-specific MBCs that are predominantly IgG + from infancy to adulthood. In response to acute febrile malaria, Pf- specific IgM B cells increase in frequency and upregulate activation and co-stimulatory markers. B cell receptor (BCR) analysis showed that Pf -specific IgM B cells are somatically hypermutated at levels comparable to HA-specific IgG B cells. Finally, IgM antibodies from the plasma of malaria-exposed individuals were comparable to IgG in inhibiting Pf blood-stage growth in vitro , and significantly better at enhancing phagocytosis of Pf merozoites, suggesting that IgM may protect through both direct neutralization and opsonization. Thus, somatically hypermutated Pf -specific IgM MBCs dominate in early life, are activated and expand during acute malaria and are associated with plasma IgM that inhibits parasite growth in vitro .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122688,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9416,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":467982,"name":"Ababacar Diouf","orcid":"0000-0003-2259-6522","position":1,"is_corresponding":false},{"id":329084,"name":"Kazutoyo Miura","orcid":"0000-0003-4455-2432","position":2,"is_corresponding":false},{"id":564431,"name":"Kristin L. 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Koup","orcid":"0000-0002-3090-7282","position":17,"is_corresponding":false},{"id":513631,"name":"Eric O. Long","orcid":"0000-0002-7793-3728","position":18,"is_corresponding":false},{"id":218075,"name":"Adrian B. McDermott","orcid":"0000-0003-0616-9117","position":19,"is_corresponding":false},{"id":260447,"name":"Peter D. Crompton","orcid":"0000-0001-5629-0412","position":20,"is_corresponding":false},{"id":260426,"name":"Christine S. Hopp","orcid":"0000-0002-0528-9531","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T23:14:55.385653Z","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":[]}