Copyright: © 2015 Kim et al. BXD2 mice spontaneously develop autoantibodies and subsequent glomerulonephritis, offering a useful animal model to study autoimmune lupus. Although initial studies showed a critical contribution of IL-17 and Th17 cells in mediating autoimmune B cell responses in BXD2 mice, the role of follicular helper T (Tfh) cells remains incompletely understood. We found that both the frequency of Th17 cells and the levels of IL-17 in circulation in BXD2 mice were comparable to those of wild-type. By contrast, the frequency of PD-1 < sup > + < /sup > CXCR5 < sup > + < /sup > Tfh cells was significantly increased in BXD2 mice compared with wild-type mice, while the frequency of PD-1 < sup > + < /sup > CXCR5 < sup > + < /sup > Foxp3 < sup > + < /sup > follicular regulatory T (Tfr) cells was reduced in the former group. The frequency of Tfh cells rather than that of Th17 cells was positively correlated with the frequency of germinal center B cells as well as the levels of autoantibodies to dsDNA. More importantly, CXCR5 < sup > + < /sup > CD4 < sup > + < /sup > T cells isolated from BXD2 mice induced the production of IgG from naïve B cells in an IL-21-dependent manner, while CCR6 < sup > + < /sup > CD4 < sup > + < /sup > T cells failed to do so. These results together demonstrate that Tfh cells rather than Th17 cells contribute to the autoimmune germinal center reactions in BXD2 mice.
Kim, Y. U., Lim, H., Jung, H. E., Wetsel, R. A., & Chung, Y. (2015). Regulation of autoimmune germinal center reactions in lupus-prone BXD2 mice by follicular helper T cells. PLoS ONE, 10(3). https://doi.org/10.1371/journal.pone.0120294