Characterization of ectopic lymphoid structures in different types of acute renal allograft rejection

Summary We hypothesize that T cells such as interleukin (IL)‐21 + B cell lymphoma 6 (BCL6) + T follicular helper cells can regulate B cell‐mediated immunity within the allograft during acute T cell‐mediated rejection; this process may feed chronic allograft rejection in the long term. To investigate this mechanism, we determined the presence and activation status of organized T and B cells in so‐called ectopic lymphoid structures (ELSs) in different types of acute renal allograft rejection. Biopsies showing the following primary diagnosis were included: acute/active antibody‐mediated rejection, C4d + (a/aABMR), acute T cell‐mediated rejection grade I (aTCMRI) and acute T cell‐mediated rejection grade II (aTCMRII). Paraffin sections were stained for T cells (CD3 and CD4), B cells (CD20), follicular dendritic cells (FDCs, CD23), activated B cells (CD79A), immunoglobulin (Ig)D, cell proliferation (Ki67) and double immunofluorescent stainings for IL‐21 and BCL6 were performed. Infiltrates of T cells were detected in all biopsies. In aTCMRI, B cells formed aggregates surrounded by T cells. In these aggregates, FDCs, IgD and Ki67 were detected, suggesting the presence of ELSs. In contrast, a/aABMR and aTCMRII showed diffuse infiltrates of T and B cells but no FDCs and IgD. IL‐21 was present in all biopsies. However, co‐localization with BCL6 was observed mainly in aTCMRI biopsies. In conclusion, ELSs with an activated phenotype are found predominantly in aTCMRI where T cells co‐localize with B cells. These findings suggest a direct pathway of B cell alloactivation at the graft site during T cell mediated rejection.