Volume 4 Issue 11
Nov.  2013
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Xiaoran Wu, Yi Tan, Qiao Xing, Shengdian Wang. IL-21 accelerates xenogeneic graft-versus-host disease correlated with increased B-cell proliferation[J]. Protein&Cell, 2013, 4(11): 863-871. doi: 10.1007/s13238-013-3088-8
Citation: Xiaoran Wu, Yi Tan, Qiao Xing, Shengdian Wang. IL-21 accelerates xenogeneic graft-versus-host disease correlated with increased B-cell proliferation[J]. Protein&Cell, 2013, 4(11): 863-871. doi: 10.1007/s13238-013-3088-8

IL-21 accelerates xenogeneic graft-versus-host disease correlated with increased B-cell proliferation

doi: 10.1007/s13238-013-3088-8
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This work was supported by grants from the National Natural Science Foundation of China (Grant No. 81000920).

  • Received Date: 2013-09-18
  • Rev Recd Date: 2013-10-17
  • Graft-versus-host disease (GVHD) is a prevalent and potential complication of hematopoietic stem cell transplantation. An animal model, xenogeneic GVHD (X-GVHD), that mimics accurately the clinical presentation of GVHD would provide a tool for investigating the mechanism involved in disease pathogenesis. Murine models indicated that inhibiting IL-21 signaling was a good therapy to reduce GVHD by impairing T cell functions. We sought to investigate the effect of exogenous human IL-21 on the process of X-GVHD. In this study, human IL-21 was expressed by hydrodynamic gene delivery in BALB/cRag2-/- IL-2Rγc-/- (BRG) immunodeficient mice which were intravenously transplanted human peripheral blood mononuclear cells (hPBMCs). We found that human IL-21 exacerbated X-GVHD and resulted in rapid fatality. As early as 6 days after hPBMCs transplanted to BRG mice, a marked expansion of human CD19+ B cells, but not T cells, was observed in spleen of IL-21-treated mice. Compared with control group, IL-21 induced robust immunoglobulin secretion, which was accompanied by increased accumulation of CD19+ CD38high plasma cells in spleen. In addition, we demonstrated that B-cell depletion was able to ameliorate X-GVHD. These results are the first to find in vivo expansion and differentiation of human B cells in response to IL-21, and reveal a correlation between the expansion of B cells and the exacerbation of xenogeneic GVHD. Our findings show evidence of the involvement of B cells in X-GVHD and may have implications in the treatment of the disease.
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