ArticleBlood advances2017
HSC extrinsic sex-related and intrinsic autoimmune disease-related human B-cell variation is recapitulated in humanized mice.
Article in Blood advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Reporting preclinical gene therapy studies in the field of Niemann-Pick type C disease according to the ARRIVE guidelines.Orphanet journal of rare diseases · 2025Review
- T Cell Development and Responses in Human Immune System Mice.Annual review of immunology · 2025Review
- Epitope-based precision immunotherapy of Type 1 diabetes.Human vaccines & immunotherapeutics · 2023Article
- Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue.Frontiers in immunology · 2023Article
- T1D patient-derived hematopoietic stem cells are programmed to generate Tph, Tfh, and autoimmunity-associated B cell subsets in human immune system mice.Clinical immunology (Orlando, Fla.) · 2022Article
- Defects in Long-Term APC Repopulation Ability of Adult Human Bone Marrow Hematopoietic Stem Cells (HSCs) Compared with Fetal Liver HSCs.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Modeling human T1D-associated autoimmune processes.Molecular metabolism · 2022Review
- Role of the thymus in spontaneous development of a multi-organ autoimmune disease in human immune system mice.Journal of autoimmunity · 2021Article
- Central human B cell tolerance manifests with a distinctive cell phenotype and is enforced via CXCR4 signaling in hu-mice.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- HLA-Haploidentical Family Donors: The New Promise for Childhood Acute Lymphoblastic Leukaemia?Frontiers in pediatrics · 2021Review
- Reduced positive selection of a human TCR in a swine thymus using a humanized mouse model for xenotolerance induction.Xenotransplantation · 2020Article
- Human Immune System Mice With Autologous Tumor for Modeling Cancer Immunotherapies.Frontiers in immunology · 2020Review
- The development of human immune system mice and their use to study tolerance and autoimmunity.Journal of translational autoimmunity · 2019Review
- Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies.Immunological reviews · 2019Review
- Rheumatoid Arthritis-Associated Mechanisms ofJournal of clinical medicine · 2019Review
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
B cells play a major role in antigen presentation and antibody production in the development of autoimmune diseases, and some of these diseases disproportionally occur in females. Moreover, immune responses tend to be stronger in female vs male humans and mice. Because it is challenging to distinguish intrinsic from extrinsic influences on human immune responses, we used a personalized immune (PI) humanized mouse model, in which immune systems were generated de novo from adult human hematopoietic stem cells (HSCs) in immunodeficient mice. We assessed the effect of recipient sex and of donor autoimmune diseases (type 1 diabetes [T1D] and rheumatoid arthritis [RA]) on human B-cell development in PI mice. We observed that human B-cell levels were increased in female recipients regardless of the source of human HSCs or the strain of immunodeficient recipient mice. Moreover, mice injected with T1D- or RA-derived HSCs displayed B-cell abnormalities compared with healthy control HSC-derived mice, including altered B-cell levels, increased proportions of mature B cells and reduced CD19 expression. Our study revealed an HSC-extrinsic effect of recipient sex on human B-cell reconstitution. Moreover, the PI humanized mouse model revealed HSC-intrinsic defects in central B-cell tolerance that recapitulated those in patients with autoimmune diseases. These results demonstrate the utility of humanized mouse models as a tool to better understand human immune cell development and regulation.
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Registered trials
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