{"doi":"10.1073/pnas.2313672121","title":"Isotype switching in human memory B cells sets intrinsic antigen-affinity thresholds that dictate antigen-driven fates","abstract":"Memory B cells (MBCs) play a critical role in protection against homologous and variant pathogen challenge by either differentiating to plasma cells (PCs) or to germinal center (GC) B cells. The human MBC compartment contains both switched IgG + and unswitched IgM + MBCs; however, whether these MBC subpopulations are equivalent in their response to B cell receptor cross-linking and their resulting fates is incompletely understood. Here, we show that IgG + and IgM + MBCs can be distinguished based on their response to κ-specific monoclonal antibodies of differing affinities. IgG + MBCs responded only to high-affinity anti-κ and differentiated almost exclusively toward PC fates. In contrast, IgM + MBCs were eliminated by apoptosis by high-affinity anti-κ but responded to low-affinity anti-κ by differentiating toward GC B cell fates. These results suggest that IgG + and IgM + MBCs may play distinct yet complementary roles in response to pathogen challenge ensuring the immediate production of high-affinity antibodies to homologous and closely related challenges and the generation of variant-specific MBCs through GC reactions.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":431475,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":818033,"name":"Prasida Holla","orcid":"0000-0001-5479-668X","position":1,"is_corresponding":false},{"id":864652,"name":"Haewon Sohn","orcid":"0000-0002-5126-0676","position":2,"is_corresponding":false},{"id":1037771,"name":"Rachel George","orcid":"0000-0001-8473-0358","position":3,"is_corresponding":false},{"id":260427,"name":"Tuan M. Tran","orcid":"0000-0002-1928-861X","position":4,"is_corresponding":false},{"id":864653,"name":"Susan K. Pierce","orcid":"0000-0002-1484-7566","position":5,"is_corresponding":false},{"id":864651,"name":"Abhijit A. Ambegaonkar","orcid":"0000-0001-9778-7396","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T01:59:25.642507Z","pmid":"38502693","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":[]}