{"doi":"10.1101/2021.03.04.433964","title":"IgM <sup>+</sup> and IgM <sup>-</sup> memory B cells represent heterogeneous populations capable of producing class-switched antibodies and germinal center B cells upon re-challenge with <i>P. yoelii</i>","abstract":"Abstract Memory B cells (MBCs) are essential for maintaining long-term humoral immunity to infectious organisms, including Plasmodium . MBCs are a heterogeneous population whose function can be dictated by isotype or expression of particular surface proteins. Here, aided by antigen-specific B-cell tetramers, MBC populations were evaluated to discern their phenotype and function in response to infection with a non-lethal strain of P. yoelii . Infection of mice with P. yoelii 17X resulted in the production of two predominant MBC populations: somatically hypermutated isotype-switched (IgM - ) and IgM + MBCs that co-expressed CD73 and CD80 that produced antigen-specific antibodies in response to secondary infection. Re-challenge experiments indicated that IgG-producing cells dominated the recall response over the induction of IgM-secreting cells, with both populations expanding with similar timing during the secondary response. Furthermore, using ZsGreen1 expression as a surrogate for activation-induced cytidine deaminase expression alongside CD73 and CD80 co-expression, ZsGreen1 + CD73 + CD80 + IgM + MBCs gave rise to class-switched IgG-producing plasmablasts that induced comparable titers of Ag-specific Abs as their IgM - counterparts after adoptive transfer and infection with P. yoelii . Moreover, ZsGreen1 + CD73 + CD80 + IgM + and IgM - MBCs differentiated into B cells with a germinal center phenotype after adoptive transfer. A third population of B cells (ZsGreen1 - CD73 - CD80 - IgM - ) that emerges after infection responded poorly to reactivation in vitro and in vivo, indicating that these cells do not represent a population of MBCs. Together these data indicated that MBC function is not defined by immunoglobulin isotype, nor does co-expression of key surface markers limit the potential fate of MBCs after recall. Summary IgM + and IgM - MBCs that co-express CD73 and CD80 can differentiate into plasmablasts and GC B cells after re-challenge with P. yoelii .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220372,"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":0.9553,"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":820237,"name":"Jonathan J. Bauer","orcid":null,"position":1,"is_corresponding":false},{"id":239786,"name":"Juhyung Lee","orcid":"0000-0002-3638-1496","position":2,"is_corresponding":false},{"id":820238,"name":"Enatha Ntirandekura","orcid":null,"position":3,"is_corresponding":false},{"id":402667,"name":"Jason S. Stumhofer","orcid":"0000-0003-2583-0206","position":4,"is_corresponding":false},{"id":640108,"name":"Susie L. Brown","orcid":"0000-0002-2116-6398","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-18T23:53:46.965811Z","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":[]}