biostudies-literatureUnknown16Lin EVNSG-SGM3 humanized mouse models are well-suited for studying human immune physiology but are technically challenging and expensive. We previously characterized a simplified NSG-SGM3 mouse, engrafted with human donor CD34⁺ hematopoietic stem cells without receiving prior bone marrow ablation or human secondary lymphoid tissue implantation, that still retains human mast cell- and basophil-dependent passive anaphylaxis responses. Its capacities for human antibody production and human B cell maturation, however, remain unknown. Here, we show that NSG-SGM3 mice engrafted without prior marrow ablation spontaneously produce all human antibodies, including IgE, without deliberate sensitization. These human IgE antibodies are polyclonal with unexpected specificities to diverse allergens,Frontiers in immunology1628194https://www.ebi.ac.uk/biostudies/studies/S-EPMC12414937biostudies-literatureEngrafted NSG-SGM3 humanized mice spontaneously produce human immunoglobulins including IgE.PMC12414937Sokol KABochner BSLin EVArce BDispenza MCKrier-Burris RAVilela NMHamilton RGfalseEngrafted NSG-SGM3 humanized mice spontaneously produce human immunoglobulins including IgE.NSG-SGM3 humanized mouse models are well-suited for studying human immune physiology but are technically challenging and expensive. We previously characterized a simplified NSG-SGM3 mouse, engrafted with human donor CD34⁺ hematopoietic stem cells without receiving prior bone marrow ablation or human secondary lymphoid tissue implantation, that still retains human mast cell- and basophil-dependent passive anaphylaxis responses. Its capacities for human antibody production and human B cell maturation, however, remain unknown. Here, we show that NSG-SGM3 mice engrafted without prior marrow ablation spontaneously produce all human antibodies, including IgE, without deliberate sensitization. These human IgE antibodies are polyclonal with unexpected specificities to diverse allergens,2025-01-01T00:00:00Z20252026-06-03T05:59:17.291Z2026-04-25T03:19:00.296ZS-EPMC124149374092771010.3389/fimmu.2025.1628194