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Research Article: Targeted replacement of human ?? TCR in mice enhances antigen-specific B cell immunity

Date Published: 2026-06-17

Abstract:
The humanized (Hu) gamma delta (??) T cell receptor (TCR) -T1 (?? HuTCR-T1) mouse model represents a novel and versatile platform for investigating human-like immune responses in vivo . In this study, we assessed the adaptive and humoral immune responses of ?? HuTCR-T1 mice compared with wild-type (WT) counterparts following immunization with collagen and keratin antigens. ?? HuTCR-T1 mice exhibited markedly enhanced B cell activity, as demonstrated by a significant increase in antigen-specific antibody-secreting cells (ASCs), elevated serum titers of antigen-specific IgG, IgA, and IgE, and expansion of both plasma and memory B cell populations within spleen and blood tissues. In addition to the amplified B cell responses, ?? HuTCR-T1 mice displayed a distinct and dynamic cytokine profile, characterized by increased production of interleukin (IL)-4, IL-6, IL-10, IL-17, TGF?, IFN?, and TNF?, reflecting a balanced pro- and anti-inflammatory immune landscape. Importantly, serum levels of anti-ANA antibodies remained below the detection threshold. Collectively, these findings demonstrate that human ?? T cells modulate adaptive and humoral immunity through both direct cellular interactions and cytokine-driven mechanisms that promote B cell maturation, activation, and class switching. This work advances our understanding of ?? T cells as critical regulators of immune homeostasis and highlights the ?? HuTCR-T1 model as a valuable translational resource for preclinical studies.

Introduction:
The immune system is a highly complex network of cells and molecular pathways evolved to defend the host against infections and diseases. Among its central components are B and T cells, each performing distinct but interconnected roles. B cells are the essential effectors of an adaptive immune system and their functions that include antibody production, antigen presentation, and the generation of immunological memory ( 1 ). A specialized subset of T cells, including gamma delta (??) T cells, contribute to immune…

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