ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Studies of lymphocyte reconstitution in a humanized mouse model reveal a requirement of T cells for human B cell maturation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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73 citing papers in PubMed, 113 citations in OpenAlex.
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- Preclinical models in the study of lymph node metastasis.Journal of Zhejiang University. Science. B · 2025Review
- The Impact of Animal Models and Strain Standardization on the Evaluation of Tuberculosis Vaccine Efficacy.Vaccines · 2025Review
- Follicular helper- and peripheral helper-like T cells drive autoimmune disease in human immune system mice.eLife · 2025Article
- Efficient generation of human immune system rats using human CD34Stem cell reports · 2024Article
- KSHV infection of B cells primes protective T cell responses in humanized mice.Nature communications · 2024Article
- Inhibition of caspase pathways limits CD4Retrovirology · 2024Article
- A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies.bioRxiv : the preprint server for biology · 2024Article
- A novel humanized mouse model for HIV and tuberculosis co-infection studies.Frontiers in immunology · 2024Article
- Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors.Journal of visualized experiments : JoVE · 2022Article
- 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
- Advanced Immune Cell Profiling by Multiparameter Flow Cytometry in Humanized Patient-Derived Tumor Mice.Cancers · 2022Article
- Modeling human T1D-associated autoimmune processes.Molecular metabolism · 2022Review
- Positive and negative selection shape the human naive B cell repertoire.The Journal of clinical investigation · 2022Article
- Cabozantinib sensitizes microsatellite stable colorectal cancer to immune checkpoint blockade by immune modulation in human immune system mouse models.Frontiers in oncology · 2022Article
- An immune-humanized patient-derived xenograft model of estrogen-independent, hormone receptor positive metastatic breast cancer.Breast cancer research : BCR · 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
- Development of a humanized mouse model to analyze antibodies specific for human leukocyte antigen (HLA).PloS one · 2021Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The hematopoietic humanized mouse (hu-mouse) model is a powerful resource to study and manipulate the human immune system. However, a major and recurrent issue with this model has been the poor maturation of B cells that fail to progress beyond the transitional B cell stage. Of interest, a similar problem has been reported in transplant patients who receive cord blood stem cells. In this study, we characterize the development of human B and T cells in the lymph nodes (LNs) and spleen of BALB/c-Rag2(null)Il2rγ(null) hu-mice. We find a dominant population of immature B cells in the blood and spleen early, followed by a population of human T cells, coincident with the detection of LNs. Notably, in older mice we observe a major population of mature B cells in LNs and in the spleens of mice with higher T cell frequencies. Moreover, we demonstrate that T cells are necessary for B cell maturation, as introduction of autologous human T cells expedites the appearance of mature B cells, whereas in vivo depletion of T cells retards B cell maturation. The presence of the mature B cell population correlates with enhanced IgG and Ag-specific responses to both T cell-dependent and T cell-independent challenges, indicating their functionality. These findings enhance our understanding of human B cell development, provide increased details of the reconstitution dynamics of hu-mice, and validate the use of this animal model to study mechanisms and treatments for the similar delay of functional B cells associated with cord blood transplantations.
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