{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:44:15Z","timestamp":1793738655068,"version":"4.6.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"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>Immune-humanized mouse models are indispensable tools for evaluating human immune responses and testing immune-based therapies; however, the induction of robust human antigen-specific immunoglobulin G (IgG) production remains limited due to species-specific incompatibilities. To investigate how human interleukin-4 (IL-4) promotes antibody responses, we employed NOG-hIL-4 transgenic mice (NOG-hIL-4-Tg), which constitutively express human IL-4, and transplanted them with human peripheral blood mononuclear cells (PBMCs). Flow cytometry, histological analysis, and next-generation sequencing were used to assess human lymphocyte maintenance, receptor repertoire diversity, class switching, and antigen-specific responses following immunization with peptide antigens. Sustained human B cell maintenance correlated with defined supraphysiological ranges of plasma hIL-4 concentrations. T and B cell receptor repertoire analyses demonstrated stable clonal diversity for one month after engraftment, followed by contraction by three months. Immunoglobulin repertoire profiling revealed IL-4\u2013dependent class switching to IgG, with early predominance of IgG3 that declined over time and a gradual increase in IgG1, though subclass distribution varied among donors. Immunization induced antigen-reactive IgG, although many clones displayed low-affinity or cross-reactive binding, consistent with limited affinity maturation. Histological examination revealed tertiary lymphoid structure\u2013like accumulations of human B and T cells within the spleen, without fully developed germinal centers. These findings demonstrate that human IL-4 expression in NOG-hIL-4-Tg mice supports human B cell survival, class switching, and partial IgG maturation, providing a relevant platform for studying human humoral immunity and evaluating antibody-based immunotherapies.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1670682","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:19:36Z","timestamp":1764152376000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Human interleukin-4-dependent facilitation of human IgG production in PBL-NOG-hIL-4-Tg 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