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Publication : A novel mouse model for tracking the fate of CXCR5-expressing T cells.

First Author  Takebe T Year  2018
Journal  Biochem Biophys Res Commun Volume  495
Issue  2 Pages  1642-1647
PubMed ID  29223395 Mgi Jnum  J:270146
Mgi Id  MGI:6277205 Doi  10.1016/j.bbrc.2017.12.029
Citation  Takebe T, et al. (2018) A novel mouse model for tracking the fate of CXCR5-expressing T cells. Biochem Biophys Res Commun 495(2):1642-1647
abstractText  The germinal center (GC) reaction, a critical process in the humoral immune response, requires follicular helper T (Tfh) cells. Tfh cells express the master transcription factor Bcl6 and chemokine receptor CXCR5, which enable them to migrate from the T cell zone to B cell follicles and interact with GC B cells. However, CXCR5 is downregulated when Tfh cells become memory cells. Therefore, it is difficult to track Tfh cells continuously in vivo. In this study, we generated a mouse strain, Cxcr5(CreERT2)R26(Tomato), in which the fluorescent protein tdTomato is inducibly expressed in CXCR5(+) cells by tamoxifen administration. After the oral administration of tamoxifen, most Tfh cells in Peyer's patches (PP) from Cxcr5(CreERT2)R26(Tomato) mice were tdTomato(+). To track antigen-specific Tfh cells in vivo, OVA-specific OT-II T cells derived from Cxcr5(CreERT2)R26(Tomato) mice were transferred to wild-type mice, and the recipient mice were immunized with OVA followed by tamoxifen administration. CXCR5(+) T cells became tdTomato(+) and were mainly located in B cell follicles and GC areas 8 days after immunization. Four weeks after immunization, tdTomato(+) OT-II T cells migrated from B cell follicles to the T-B border area and T cell zone after CXCR5 downregulation and CCR7 upregulation. These results indicate that Cxcr5(CreERT2)R26(Tomato) mice are a useful tool for studying the cell fate of differentiated Tfh cells in vivo and therefore have implications for the development of therapeutic strategies for infectious and autoimmune diseases.
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