Characterization of intra-graft B cells during renal allograft rejection.

Intra-graft CD20(+) B-cell clusters are found during acute rejection of renal allografts and correlate with graft recovery following rejection injury. Here using archived kidney tissue we conducted immunohistochemical studies to measure specific subsets of pathogenic B cells during graft rejection. Cluster-forming CD20(+) B cells in the rejected graft are likely derived from the recipient and are composed of mature B cells. These cells are activated (CD79a(+)), and present MHC Class II antigen (HLADR(+)) to CD4(+) T cells. Some of these clusters contained memory B cells (CD27(+)) and they did not correlate with intra-graft C4d deposition or with detection of donor-specific antibody. Further, several non-cluster forming CD20(-) B-lineage CD38(+) plasmablasts and plasma cells were found to infiltrate the rejected grafts and these cells strongly correlated with circulating donor-specific antibody, and to a lesser extent with intra-graft C4d. Both CD20(+) B cells and CD38(+) cells correlated with poor response of the rejection to steroids. Reduced graft survival was associated with the presence of CD20 cells in the graft. In conclusion, a specific subset of early lineage B cells appears to be an antigen-presenting cell and which when present in the rejected graft may support a steroid-resistant T-cell-mediated cellular rejection. Late lineage interstitial plasmablasts and plasma cells may also support humoral rejection. These studies suggest that detailed analysis of interstitial cellular infiltrates may allow better use of B-cell lineage specific treatments to improve graft outcomes.