Transplantation of human spleen into immunodeficient NOD/SCID IL2Rγ^null mice generates humanized mice that improve functional B cell development

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.