BAFF blockade attenuates acute graft-versus-host disease directly via the dual regulation of T- and B-cell homeostasis

INTRODUCTION: B-cell-activating factor (BAFF) is associated with donor-specific antibodies and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the effects of BAFF on T-cell physiological function have not been fully elucidated in acute GVHD. METHODS: We examined the effects of belimumab, a monoclonal antibody targeting BAFF, for the treatment of acute GVHD. We examined the effects of T cells and B cells separately when inducing GVHD in mouse model. RESULTS: Therapeutic functional manipulation of endogenous BAFF can improve acute GVHD during the early post-transplant period. In this study, BAFF was shown to increase the proportions of CD4(+)IL-17(+), CD4(+)IL-6(+) Th17, and CD4(+)IFN-γ(+) Th1 cells and to reduce the proportion of regulatory T (Treg) cells. Furthermore, the belimumab therapy group showed increased B220(+)IgD(+)IgM(+) mature B cells but decreased B220(+)IgD(−)IgM(−) memory B cells, B220(+)Fas(+)GL-7(+) germinal center formation, and B220(+)IgD(−)CD138(+) plasma cells. These results indicate that BAFF can alleviate acute GVHD by simultaneously regulating T and B cells. Interestingly, the BAFF level was higher in patients with acute GVHD after HSCT compared with patients receiving chemotherapy. CONCLUSION: This study suggests that BAFF blockade might modulate CD4 +T-cell-induced acute GVHD early after allo-HSCT and the possibility of simultaneously controlling chronic GVHD, which may appear later after allo-HSCT.