{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:57:43Z","timestamp":1781672263471,"version":"3.54.5"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"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>\n                    The humanized (Hu) gamma delta (\u03b3\u03b4) T cell receptor (TCR) -T1 (\u03b3\u03b4 HuTCR-T1) mouse model represents a novel and versatile platform for investigating human-like immune responses\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In this study, we assessed the adaptive and humoral immune responses of \u03b3\u03b4 HuTCR-T1 mice compared with wild-type (WT) counterparts following immunization with collagen and keratin antigens. \u03b3\u03b4 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, \u03b3\u03b4 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\u03b2, IFN\u03b3, and TNF\u03b1, 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 \u03b3\u03b4 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 \u03b3\u03b4 T cells as critical regulators of immune homeostasis and highlights the \u03b3\u03b4 HuTCR-T1 model as a valuable translational resource for preclinical studies.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1734493","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:49:48Z","timestamp":1781671788000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted replacement of human \u03b3\u03b4 TCR in mice enhances antigen-specific B cell immunity"],"prefix":"10.3389","volume":"17","author":[{"given":"Husheem","family":"Michael","sequence":"first","affiliation":[{"name":"Cell Biology and Immunology, InGenious Targeting Laboratory","place":["Holbrook, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pitre","sequence":"additional","affiliation":[{"name":"Cell Biology and Immunology, InGenious Targeting Laboratory","place":["Holbrook, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene W.","family":"Weng","sequence":"additional","affiliation":[{"name":"Cell Biology and Immunology, InGenious Targeting Laboratory","place":["Holbrook, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikaela M.","family":"Vallas","sequence":"additional","affiliation":[{"name":"Cell Biology and Immunology, InGenious Targeting Laboratory","place":["Holbrook, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Chen","sequence":"additional","affiliation":[{"name":"Cell Biology and Immunology, InGenious Targeting Laboratory","place":["Holbrook, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Sheiffele","sequence":"additional","affiliation":[{"name":"Cell Biology and Immunology, InGenious Targeting 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