Development and Characterization of a Humanized Immune System Mouse Model Using BALB/C Mice

The development of humanized mouse models has become a cornerstone in immunological research, providing a unique platform to investigate human-specific immune responses, infectious diseases, and therapeutic interventions. In this study, we aimed to establish a humanized immune system in BALB/C mice through a combination of thymectomy, gamma irradiation, and transplantation of human peripheral blood leukocytes. BALB/C mice aged ۴-۲۵ days were thymectomized to suppress native immune activity and subsequently exposed to ۸ Gy whole-body gamma irradiation. Within ۲۴ hours post-irradiation, mice received intraperitoneal injections of human leukocytes. Fourteen days after transfusion, multiple lines of evidence confirmed successful engraftment of human immune components. Human immunoglobulins were detected in serum, with IgG present in seven mice and both IgG and IgM in two mice. Peripheral blood leukocyte counts increased markedly from baseline values of ۳۰۰-۷۰۰/mm³ to ۲۵۰۰-۷۰۰۰/mm³, accompanied by the presence of immunocytes and immunoblasts in blood smears. Histological examination of spleen tissue revealed hyperplasia of red and white pulp, with infiltration of lymphocytes, macrophages, and plasma cells. Chromosomal analysis of cultured peripheral blood cells demonstrated a human karyotype (۴۶ chromosomes), further validating engraftment. Notably, no graft-versus-host (GVH) reaction was observed, which may be explained by major histocompatibility complex (MHC) compatibility or tolerance mechanisms. Collectively, these findings demonstrate the feasibility of generating BALB/C mice with functional human immune systems. This model provides a valuable tool for studying human-specific pathogens such as HIV and Epstein-Barr virus, evaluating immune responses, and testing novel immunomodulatory therapies.

کلیدواژه ها:

Immune system ، Mouse ، Humanization