title: Transplantation of human spleen into immunodeficient NOD/SCID IL2Rγ(null) mice generates humanized mice that improve functional B cell development.
abstract: We previously generated humanized TB34N mice that received human fetal thymus (T), bone tissue (B) and fetal liver-derived (FL)-CD34(+) cells (34) in immunodeficient, NOD/SCID IL2Rγ(null) (N) mice. Although humanized TB34N mice had excellent hematopoiesis, here, we sought to further improve this model by additional transplantation of human spleen tissue (S) as a secondary hematopoietic tissue (TBS34N). The human spleen grafts were enlarged and differentiated into a similar morphology of adult humans, including follicular lymphoid structures with T- and B-cells. The TBS34N mice mimicked mature human immune system (HIS): mature T- and B-cells and follicular dendritic cells; activated germinal center B-cells expressing CD71, BR3(+) cells, memory B-cells and activation-induced cytidine deaminase(+) B-cells; CD138(+) plasma cells were enriched in the mouse spleen. HBsAg-specific hIgG antibodies were secreted into the sera of all TBS34N mice upon immunization with HBsAg. Taken together, the humanized TBS34N mice improved mature HIS and achieved adaptive antibody responses.
authors.affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Yun Shin
authors.initials: YS
authors.lastname: Chung
authors.affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Son
authors.affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Bongkum
authors.initials: B
authors.lastname: Choi
authors.affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea; Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Berm
authors.initials: JB
authors.lastname: Park
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Republic of Korea. Electronic address: tcell@ewha.ac.kr.
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea; Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: kmhyj111@gmail.com.
authors.forename: Sung Joo
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D020566:Dendritic Cells, Follicular / Q000276:immunology; D016332:Fetal Tissue Transplantation / Q000379:methods*; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D023421:Models, Animal; D011990:Receptors, Transferrin / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology* / Q000637:transplantation*; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D006514:Hepatitis B Surface Antigens; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D011990:Receptors, Transferrin
keywords: Bone; CD34(+) cells; Hematopoiesis; Humanized mice; Spleen; Thymus