Development of human B cells and antibodies following human hematopoietic stem cell transplantation to Rag2−/−γc−/− mice

Tanner, A.R. Martinez-Fernandez C.E.; Hallam, Steven J.; Nielsen, Stanton J.; Cuadra, German I.; Berges, Bradford K.

doi:10.1016/j.trim.2015.03.002

Cited by 2 publications

(2 citation statements)

References 35 publications

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“…In contrast to the above-discussed findings, HIV-specific CD8 + T cells are present in chronically HIV-infected NSG mice, and their depletion at this later time point resulted in an increase in viral load (67). In addition, we did not detect any human HIV-specific IgG at 12 and 20 wk p.i., consistent with published data (68). The lack of human HIV-specific IgG is largely explained by the predominance of immature B cells (24).…”

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confidence: 91%

Differential Dynamics of HIV Infection in Humanized MISTRG versus MITRG Mice

Ivic

Rochat

et al. 2017

ImmunoHorizons

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Humanized mice are a powerful tool to study HIV in vivo. The recently generated mouse strains MITRG and MISTRG, which differ in human SIRPα expression, support an improved human myeloid lineage development from human hematopoietic stem and progenitor cells. The rationale of the study was the characterization of the two mouse strains during an HIV infection with CCR5- and CXCR4-tropic viruses. Upon HIV infection, we observed HIV dissemination and sustained viral load over 20 wk in peripheral blood in both reconstituted mouse strains. However, HIV RNA levels were significantly lower in MITRG mice compared with MISTRG mice during the first 8 wk postinfection. HIV-infected MISTRG mice showed lymphocyte activation and changes in lymphocyte subsets in blood and spleen, recapitulating hallmarks of HIV infection in humans. Depletion of murine tissue-resident macrophages in MITRG mice led to significantly elevated viral loads, and lymphocyte levels were similar to those in HIV-infected MISTRG mice. Depletion of CD8+ T cells in MISTRG mice before HIV infection resulted in substantially decreased CD4+ T cell levels, indicating functionality of human CD8+ T cells; depletion of CD4+CD8+ thymocytes may have contributed, in part, to the latter finding. In summary, MITRG and MISTRG mice represent novel HIV mouse models, despite differential HIV dynamics.

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confidence: 91%

Differential Dynamics of HIV Infection in Humanized MISTRG versus MITRG Mice

Ivic

Rochat

et al. 2017

ImmunoHorizons

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“…The data concerning Ig class switching in hu mice are controversial. IgG could not be detected at week 12 post-transplantation in one study [17] and only in about half of animals in another study [19]. In contrast, Traggiai et al detected IgG, albeit to various degrees, in older hu mice [4] and Lang et al showed increasing levels of IgG between week 16 and 24 post-transplantation [14], indicating class switching.…”

Section: Discussionmentioning

confidence: 99%

Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells

Audigé

Rochat

et al. 2017

BMC Immunol

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BackgroundHumanized mice (hu mice) are based on the transplantation of hematopoietic stem and progenitor cells into immunodeficient mice and have become important pre-clinical models for biomedical research. However, data about their hematopoiesis over time are scarce. We therefore characterized leukocyte reconstitution in NSG mice, which were sublethally irradiated and transplanted with human cord blood-derived CD34+ cells at newborn age, longitudinally in peripheral blood and, for more detailed analyses, cross-sectionally in peripheral blood, spleen and bone marrow at different time points.ResultsHuman cell chimerism and absolute human cell count decreased between week 16 and 24 in the peripheral blood of hu mice, but were stable thereafter as assessed up to 32 weeks. Human cell chimerism in spleen and bone marrow was maintained over time. Notably, human cell chimerism in peripheral blood and spleen as well as bone marrow positively correlated with each other. Percentage of B cells decreased between week 16 and 24, whereas percentage of T cells increased; subsequently, they levelled off with T cells clearly predominating at week 32. Natural killer cells, monocytes and plasmacytoid dendritic cells (DCs) as well as CD1c + and CD141+ myeloid DCs were all present in hu mice. Proliferative responses of splenic T cells to stimulation were preserved over time. Importantly, the percentage of more primitive hematopoietic stem cells (HSCs) in bone marrow was maintained over time.ConclusionsOverall, leukocyte reconstitution was maintained up to 32 weeks post-transplantation in our hu NSG model, possibly explained by the maintenance of HSCs in the bone marrow. Notably, we observed great variation in multi-lineage hematopoietic reconstitution in hu mice that needs to be taken into account for the experimental design with hu mice.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-017-0209-9) contains supplementary material, which is available to authorized users.

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Development of human B cells and antibodies following human hematopoietic stem cell transplantation to Rag2−/−γc−/− mice

Cited by 2 publications

References 35 publications

Differential Dynamics of HIV Infection in Humanized MISTRG versus MITRG Mice

Differential Dynamics of HIV Infection in Humanized MISTRG versus MITRG Mice

Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells

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