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

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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.

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Acknowledgments

We thank Dr. Jason Baxter and the Department of Obstetrics and Gynecology for umbilical cord blood, Scot Fenn for technical assistance, Dr. Kishore Alugupalli for help with the Borrelia hermsii and polysaccharide antigen studies, and all other members of the Manser laboratory for indirect contributions to this work. This study was supported by a Pilot Grant to T.M. that is part of an Autoimmunity Center of Excellence Award (U19 AI056363-14, Dr. Mohammed Rostami, PI).

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  1. Department of Microbiology and Immunology, Thomas Jefferson University, 302 BLSB, 233 South 10th Street, Philadelphia, PA, 19107, USA

    Raja Vuyyuru, John Patton & Tim Manser

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  1. Raja Vuyyuru
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Correspondence to Tim Manser.

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Vuyyuru, R., Patton, J. & Manser, T. Human immune system mice: current potential and limitations for translational research on human antibody responses. Immunol Res 51, 257–266 (2011). https://doi.org/10.1007/s12026-011-8243-9

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