IL-21 accelerates xenogeneic graft-versus-host disease correlated with increased B-cell proliferation.
10.1007/s13238-013-3088-8
- Author:
Xiaoran WU
1
;
Yi TAN
;
Qiao XING
;
Shengdian WANG
Author Information
1. Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
- Publication Type:Journal Article
- MeSH:
Animals;
B-Lymphocytes;
immunology;
metabolism;
pathology;
Cell Differentiation;
Cell Proliferation;
DNA-Binding Proteins;
deficiency;
Female;
Graft vs Host Disease;
blood;
genetics;
immunology;
metabolism;
Heterografts;
immunology;
Humans;
Immunoglobulin G;
metabolism;
Immunoglobulin M;
metabolism;
Interleukins;
genetics;
immunology;
Male;
Mice;
Mice, Inbred BALB C;
Plasmids;
genetics
- From:
Protein & Cell
2013;4(11):863-871
- CountryChina
- Language:English
-
Abstract:
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/c-Rag2⁻/⁻ 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⁺ CD38(high) 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.
