Regulation of autoimmune germinal center reactions in lupus-prone BXD2 mice by follicular helper T cells

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Abstract

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.

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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

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