B cells differentially regulate acute and chronic cardiac, renal, and skin allograft rejection (145.42)

Abstract

Abstract T cells contribute to both acute and chronic allograft rejection, but the roles of B cells and alloantibody are less clear. Therefore, CD20 and CD19 mAbs were used to deplete mature or total B cells, respectively, in mice before allografting. Both CD20 and CD19 mAbs effectively depleted mature B cells, but CD19 mAb also depleted >70% of CD138+ plasma cells in flow cytometry assays, as well as >66% of Ab-secreting cells in ELISPOT assays. Consequently, CD19 mAb treatment depleted serum IgG levels by 80% in naïve mice, while CD20 mAb did not. Neither CD20 nor CD19 mAb treatment affected acute cardiac allograft rejection, with all grafts rejected within 7-9 days. However, CD19 mAb treatment prevented the generation of allo-IgG. In a second model of rejection, treatment with CD19 mAb before renal transplant significantly delayed and prevented chronic renal allograft rejection, reduced kidney pathology, and abrogated the development of allo-IgG, while CD20 mAb did not. In additional experiments, CD19 mAb treatment also depleted pre-existing allo-IgG levels in serum. In a third allograft model, pretreatment with CD20 mAb exacerbated acute skin allograft rejection and augmented the proliferation of adoptively transferred alloantigen-specific CD4+ T cells by 2-fold, indicating that B cells negatively regulate acute skin graft rejection and CD4+ T cell responses. Thus, depending on the nature of the allograft, B cells can either positively or negatively regulate allograft rejection.