{"doi":"10.4049/jimmunol.2300156","title":"VH2+ Antigen-Experienced B Cells in the Cerebrospinal Fluid Are Expanded and Enriched in Pediatric Anti-NMDA Receptor Encephalitis","abstract":"Pediatric and adult autoimmune encephalitis (AE) are often associated with Abs to the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor (NMDAR). Very little is known regarding the cerebrospinal fluid humoral immune profile and Ab genetics associated with pediatric anti-NMDAR-AE. Using a combination of cellular, molecular, and immunogenetics tools, we collected cerebrospinal fluid from pediatric subjects and generated 1) flow cytometry data to calculate the frequency of B cell subtypes in the cerebrospinal fluid of pediatric subjects with anti-NMDAR-AE and controls, 2) a panel of recombinant human Abs from a pediatric case of anti-NMDAR-AE that was refractory to treatment, and 3) a detailed analysis of the Ab genes that bound the NR1 subunit of the NMDAR. Ag-experienced B cells including memory cells, plasmablasts, and Ab-secreting cells were expanded in the pediatric anti-NMDAR-AE cohort, but not in the controls. These Ag-experienced B cells in the cerebrospinal fluid of a pediatric case of NMDAR-AE that was refractory to treatment had expanded use of variable H chain family 2 (VH2) genes with high somatic hypermutation that all bound to the NR1 subunit of the NMDAR. A CDR3 motif was identified in this refractory case that likely drove early stage activation and expansion of naive B cells to Ab-secreting cells, facilitating autoimmunity associated with pediatric anti-NMDAR-AE through the production of Abs that bind NR1. These features of humoral immune responses in the cerebrospinal fluid of pediatric anti-NMDAR-AE patients may be relevant for clinical diagnosis and treatment.","journal":"The Journal of Immunology","year":2023,"id":379012,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":686175,"name":"Chad Smith","orcid":"0000-0002-6949-995X","position":1,"is_corresponding":false},{"id":1143912,"name":"Hannah Greenberg","orcid":null,"position":2,"is_corresponding":false},{"id":727293,"name":"Patricia Plumb","orcid":"0000-0002-7357-9303","position":3,"is_corresponding":false},{"id":1143474,"name":"Alyssa Guzman","orcid":"0009-0003-0164-7412","position":4,"is_corresponding":false},{"id":1143913,"name":"Key M. Tse","orcid":null,"position":5,"is_corresponding":false},{"id":24017,"name":"Ding Chen","orcid":null,"position":6,"is_corresponding":false},{"id":1143475,"name":"Wei Zhang","orcid":"0000-0002-4196-6704","position":7,"is_corresponding":false},{"id":1143914,"name":"M Morgan","orcid":null,"position":8,"is_corresponding":false},{"id":1143476,"name":"Haley E. Speed","orcid":"0000-0001-5562-4468","position":9,"is_corresponding":false},{"id":397549,"name":"Craig M. Powell","orcid":"0000-0001-5451-2165","position":10,"is_corresponding":false},{"id":1143477,"name":"Sushobhna Batra","orcid":"0000-0002-0964-975X","position":11,"is_corresponding":false},{"id":555625,"name":"Lindsay G. Cowell","orcid":"0000-0003-1617-8244","position":12,"is_corresponding":false},{"id":263518,"name":"Scott Christley","orcid":"0000-0002-9889-1221","position":13,"is_corresponding":false},{"id":494117,"name":"Steven Vernino","orcid":"0000-0001-7799-8495","position":14,"is_corresponding":false},{"id":902779,"name":"Kyle Blackburn","orcid":"0000-0001-5227-153X","position":15,"is_corresponding":false},{"id":226912,"name":"Benjamin Greenberg","orcid":"0000-0002-2091-8201","position":16,"is_corresponding":false},{"id":261145,"name":"Nancy Monson","orcid":null,"position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T01:16:52.622552Z","pmid":"37712756","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":[]}