Critical assessment of human antibody generation in humanized mouse models

• Humanized mice have normal early human B-cell development.
• B cells in the periphery of humanized mice are immature and B1-like.
• The production of antibodies in humanized mice is lower than in human.
• Class-switching and affinity maturation are limited in humanized mice.
• HLA-restriction, human cytokines and organized germinal centers are required.

Immunodeficient mice reconstituted with human hematopoietic stem cells provide a small-animal model for the study of development and function of human hematopoietic cells in vivo. However, in the current models, the immune response, and especially the humoral response by the human immune cells is far from optimal. The B cells found in these mice exhibit an immature and abnormal phenotype correlating with a reduced capacity to produce antigen-specific affinity matured antibodies upon infection or immunization. Herein, we review the current state of knowledge of development, function and antibody production of human B cells and discuss the obstacles for the improvement of these models.