Human immune system mice: current potential and limitations for translational research on human antibody responses

Abstract

It has recently become possible to generate chimeric mice durably engrafted with many components of the human immune system (HIS mice). We have characterized the maturation and function of the B cell compartment of HIS mice. The antibody response of HIS mice to T cell-dependent B cell antigens is limited, and contributing factors may be the general immaturity of the B cell compartment, infrequent helper T cells selected on human MHC class II antigens, and incomplete reconstitution of secondary lymphoid organs and their microenvironments. In contrast, HIS mice generate protective antibody responses to the bacterium Borrelia hermsii, which acts as a T cell-independent antigen in mice, but do not respond to purified polysaccharide antigens (PPS). We speculate that the anti-B. hermsii response of HIS mice is derived from an abundant B cell subset that may be analogous to B1 B cells in mice. We suggest that failure of HIS mice to respond to PPS is due to the lack of a B cell subset that may originate from adult bone marrow and is highly dependent on human interleukin-7 for development.

Effects of lymphocyte profile on development of EBV-induced lymphoma subtypes in humanized mice

“…Numerous other groups also have reported obvious immature B-cell predominance in the periphery and spleen, especially in humanized mice reconstituted for short periods (<12 wk) (18,(34)(35)(36)(37)(38). Therefore, the predominant B cells before EBV infection in the 8w hN mice in this study are believed to be immature B cells, which will differentiate to develop mature B-cell and T-cell fractions.…”

Humanized mice: Current states and perspectives

“…The bone marrow primarily contains immature B cells that express high levels of CD10, CD24, and CD38 [31]. As expected, they do not express IgD at this immature stage.…”

“…T-independent B cell responses were also observed after a B. hermsii infection in HIS mice, though these responses were less efficient than in wild type mice. In contrast, T-independent B cell responses were not induced by the T cell-independent type 2 (TI-II) antigens, Pneumococcal polysaccharide and NP-Ficoll [31].…”

“…Nevertheless, these mice generally only weakly establish lymphoid structures capable of supporting immune functions, probably due to the lack of LTi cells [31]. T-independent B cell responses were also observed after a B. hermsii infection in HIS mice, though these responses were less efficient than in wild type mice.…”

“…In contrast, the vast majority of splenic B cells express IgM and IgD. In fact, a relatively high proportion of the IgD + B cells also express, though heterogeneously, CD10, CD24, and CD38 together with CD27, a B cell memory marker [22,31]. These "memory" B cells also express IgM.…”