{"doi":"10.1101/2022.09.23.509210","title":"Marginal Zone B Cells are Necessary for the Formation of Anti-Donor IgG After Allogeneic Sensitization","abstract":"ABSTRACT The formation of anti-MHC antibody is a significant barrier to improved outcomes in organ transplantation. Patients with pre-formed anti-HLA antibodies have limited options for suitable donors, and the formation of donor-specific anti-HLA antibodies after transplantation is a harbinger of graft rejection. Despite the recognized importance of anti-HLA antibodies, the mechanisms responsible for the differentiation of B cells after exposure to allogeneic antigen are poorly understood. In order to evaluate the differentiation of B cells in response to allogeneic antigen, we used a model of H-2 b C57/Bl6 sensitization with H-2 d antigen. We found that although the formation of anti-H-2 d IgG was robust, few class switched B cells and germinal center B cells were formed. Sensitization induced weak expression of classical memory B cell markers, but we observed populations of CD21 + and IRF4 + B cells, that corresponded to an increase in the frequency of marginal zone phenotype B cells after sensitization. Depletion of marginal zone B cells prior to sensitization resulted in a significant dimunition of anti-H-2 d IgG and also fewer germinal center B cells. These results demonstrate a previously unappreciated role for marginal zone B cells as a reservoir of alloreactive B cells that are activated by allogeneic antigen.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":304372,"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":0.9541,"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":997212,"name":"G. Cohen","orcid":"0000-0001-6652-4403","position":1,"is_corresponding":false},{"id":997748,"name":"Francis I. Ibukun","orcid":null,"position":2,"is_corresponding":false},{"id":504860,"name":"Scott M. Krummey","orcid":"0000-0002-7504-9162","position":3,"is_corresponding":false},{"id":997211,"name":"Melissa A. Kallarakal","orcid":"0009-0000-9948-3871","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-19T00:32:32.651796Z","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":[]}