{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T12:14:04Z","timestamp":1769256844056,"version":"3.49.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Aplastic anemia (AA) is a severe hematological disorder characterized by bone marrow failure and peripheral pancytopenia. Immune dysregulation plays a central role in its pathogenesis. Recent studies highlight the critical involvement of activated B cells in the immunopathology of AA, influencing both disease onset and progression. Rituximab, a monoclonal antibody targeting CD20, demonstrates therapeutic potential by modulating B cell function. Notably, immune responses and clinical manifestations differ between pediatric and female patients, affecting the efficacy and safety profile of rituximab. This\u00a0narrative review synthesizes current knowledge on B-cell involvement in AA, summarizes population-specific immunologic features, and appraises the\u00a0exploratory evidence regarding rituximab use. By integrating mechanistic insights with available clinical observations, we highlight key gaps in the literature and outline priorities for future research to inform more individualized immunomodulatory strategies in AA.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1737771","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T05:17:00Z","timestamp":1769145420000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["B cells in acquired aplastic anemia and the exploratory role of rituximab: considerations in pediatric and female patients"],"prefix":"10.3389","volume":"17","author":[{"given":"Liangwu","family":"Pan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianren","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanghui","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanming","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001347","article-title":"Treg sensitivity to FasL and relative IL-2 deprivation drive idiopathic aplastic\u00a0anemia immune dysfunction","volume":"136","author":"Lim","year":"2020","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e2304539","DOI":"10.1002\/advs.202304539","article-title":"Unbiased single-cell sequencing of hematopoietic and immune cells from aplastic anemia reveals the contributors of hematopoiesis failure and dysfunctional immune regulation","volume":"11","author":"Guo","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-022-2310-x","article-title":"Repair of dysfunctional bone marrow endothelial cells alleviates aplastic anemia","volume":"66","author":"Tang","year":"2023","journal-title":"Sci China Life Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-025-01483-4","article-title":"TGF-\u03b2 inhibition restores hematopoiesis and immune balance via bone marrow EPCs in aplastic anemia","volume":"57","author":"Zhang","year":"2025","journal-title":"Exp Mol Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000547027","article-title":"Exploration of B- and T-cell receptor repertoires reveals distinct mechanisms in pure red cell aplasia, autoimmune hemolytic anemia, and aplastic anemia","volume":"148","author":"Zhang","year":"2025","journal-title":"Acta Haematol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-022-04757-3","article-title":"HLA-G-ILT2 interaction contributes to suppression of bone marrow B cell proliferation in acquired aplastic anemia","volume":"101","author":"Sun","year":"2022","journal-title":"Ann Hematol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1182\/bloodadvances.2023010109","article-title":"Increased age-associated B cells in patients with acquired aplastic anemia correlate with IFN-\u03b3","volume":"8","author":"Solomou","year":"2024","journal-title":"Blood Adv"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.19746\/j.cnki.issn.1009-2137.2022.03.025","article-title":"Correlation between serum G-CSF level and immune function in children with aplastic anemia","volume":"30","author":"Ren","year":"2022","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"B9","doi-asserted-by":"publisher","first-page":"117492","DOI":"10.1016\/j.cca.2023.117492","article-title":"Elevated TCR-\u03b1\u03b2(+) double-negative T cells in pediatric patients with acquired aplastic anemia","volume":"548","author":"Chen","year":"2023","journal-title":"Clin Chim Acta"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1328175","article-title":"Potential role of B- and NK-cells in the pathogenesis of pediatric aplastic anemia through deep phenotyping","volume":"15","author":"Vissers","year":"2024","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1080\/08820139.2020.1770785","article-title":"CD8(+)GITR(+) T cells may negatively regulate T cell overactivation in aplastic anemia","volume":"50","author":"Huang","year":"2021","journal-title":"Immunol Invest"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-019-0270-9","article-title":"T-cell expression of Bruton's tyrosine kinase promotes autoreactive T-cell activation and exacerbates aplastic anemia","volume":"17","author":"Xia","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1590\/1806-9282.65.5.637","article-title":"Abnormal expression of b10 cell frequencies: possible relation to pathogenesis and disease severity of aplastic anemia","author":"Gu","year":"1992","journal-title":"Rev Assoc Med Bras"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.745483","article-title":"Single-cell RNA-seq of bone marrow cells in aplastic anemia","volume":"12","author":"Tonglin","year":"2021","journal-title":"Front Genet"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112137-20250224-00432","article-title":"Immune related pancytopenia: a new type of bone marrow failure","volume":"105","author":"Shao","year":"2025","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2025028723","article-title":"Imaging mass cytometry reveals the order of events in the pathogenesis of immune-mediated aplastic anemia","volume":"146","author":"Pool","year":"2025","journal-title":"Blood"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005231","article-title":"Graft\u00a0rejection markers in children undergoing hematopoietic cell transplant for\u00a0bone\u00a0marrow failure","volume":"5","author":"Sabulski","year":"2021","journal-title":"Blood Adv"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e26731","DOI":"10.1016\/j.heliyon.2024.e26731","article-title":"Insufficient phosphorylation of STAT5 in Tregs inhibits the expression of BLIMP-1 but not IRF4, reduction the proportion of Tregs in pediatric aplastic anemia","volume":"10","author":"Huang","year":"2024","journal-title":"Heliyon"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1075408","article-title":"Single-cell RNA sequencing depicts metabolic changes in children with aplastic anemia","volume":"13","author":"Zhou","year":"2023","journal-title":"Front Oncol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2356089","DOI":"10.1080\/08916934.2024.2356089","article-title":"Increased IgD and CD27 Double Negative (DN) B cell population in pediatric onset autoimmune hepatitis","volume":"57","author":"Kolachala","year":"2024","journal-title":"Autoimmunity"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1684004","article-title":"Two cases of pediatric AQP4-antibody positive neuromyelitis optica spectrum disorder successfully treated with tocilizumab","volume":"50","author":"Breu","year":"2019","journal-title":"Neuropediatrics"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/cei\/uxae076","article-title":"Unveiling immunological signatures and predictors of response to immunosuppressive therapy in acquired aplastic anemia","volume":"218","author":"Gupta","year":"2024","journal-title":"Clin Exp Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-020-04996-7","article-title":"Effects of rituximab therapy on B cell differentiation and depletion","volume":"39","author":"Bergantini","year":"2020","journal-title":"Clin Rheumatol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e12911","DOI":"10.1111\/sji.12911","article-title":"Roles of immune responses in the pathogenesis of immunorelated pancytopenia","volume":"92","author":"Xiao","year":"2020","journal-title":"Scand J Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-023-04912-6","article-title":"Immune-mediated cytopenias (IMCs) after HSCT for pediatric non-malignant disorders: epidemiology, risk factors, pathogenesis, and treatment","volume":"182","author":"Spadea","year":"2023","journal-title":"Eur J Pediatr"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e27305","DOI":"10.1016\/j.heliyon.2024.e27305","article-title":"Effect of rituximab on immune status in children with aggressive mature B-cell lymphoma\/leukemia-a prospective study from CCCG-BNHL-2015","volume":"10","author":"Dong","year":"2024","journal-title":"Heliyon"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn121090-20231229-00345","article-title":"Rituximab based treatment in pediatric Epsstain Bar Virus associated lymphocyte proliferative diseases after aplastic anemia with haplo-identical transplantation:a prospective single centre study","volume":"45","author":"Zhang","year":"2024","journal-title":"Zhonghua Xue Ye Xue Za Zhi"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112140-20220418-00340","article-title":"Comparison of the efficacy and safety of 2 low-dose rituximab regimens in the second-line treatment of primary immune thrombocytopenia in children","volume":"60","author":"Zhu","year":"2022","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112140-20250519-00431","article-title":"Association of anti-rituximab antibodies with relapse after therapy in children with frequently relapsing or steroid-dependent nephrotic syndrome","volume":"63","author":"Wang","year":"2025","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112140-20240528-00367","article-title":"Clinical study of immune-targeting combined with attenuated chemotherapy in the treatment of\u00a0children with classic Hodgkin lymphoma","volume":"62","author":"Gao","year":"2024","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e031417","DOI":"10.1161\/JAHA.123.031417","article-title":"AT1-AA is produced in offspring in response to placental ischemia and is lowered by B-cell depletion without compromising overall offspring health","volume":"13","author":"Campbell","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"B32","doi-asserted-by":"publisher","first-page":"99","DOI":"10.37349\/emed.2022.00077","article-title":"Placental CD4(+) T cells from preeclamptic patients cause autoantibodies to the angiotensin II type I receptor and hypertension in a pregnant rat model of preeclampsia","volume":"3","author":"Reeve","year":"2022","journal-title":"Explor Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13092063","article-title":"Anti-B cell strategy in nephrotic syndrome:\u00a0beyond rituximab","volume":"13","author":"Jin","year":"2025","journal-title":"Biomedicines"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112140-20240731-00537","article-title":"Efficacy and safety of rituximab in the treatment of pediatric myasthenia gravis","volume":"62","author":"Tong","year":"2024","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v9.i2.469","article-title":"Epstein-Barr virus-associated monomorphic post-transplant lymphoproliferative disorder after pediatric kidney transplantation: A case report","volume":"9","author":"Wang","year":"2021","journal-title":"World J Clin Cases"},{"key":"B36","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/bjh.13853","article-title":"Guidelines for the diagnosis and management of adult aplastic anaemia","volume":"172","author":"Killick","year":"2016","journal-title":"Br J Haematol"},{"key":"B37","first-page":"1","article-title":"Consensus for the treatment of severe aplastic anaemia in children and adolescents","author":"Masmas","year":"2023"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023011642","article-title":"Modified Delphi panel consensus recommendations for management of severe aplastic anemia","volume":"8","author":"Babushok","year":"2024","journal-title":"Blood Adv"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.14744\/nci.2024.78545","article-title":"The effect of Rituximab on B cells in pediatric autoimmune rheumatic diseases","volume":"12","author":"Baykal","year":"2025","journal-title":"North Clin Istanb"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1737771\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T05:17:05Z","timestamp":1769145425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1737771\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":39,"alternative-id":["10.3389\/fimmu.2026.1737771"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1737771","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]},"article-number":"1737771"}}