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.

Additional Metadata
Keywords Acute renal allograft rejection, B cell, Ectopic lymphoid structures, T cell, Tertiary lymphoid structures
Persistent URL dx.doi.org/10.1111/cei.13099, hdl.handle.net/1765/104418
Journal Clinical and Experimental Immunology
Citation
de Leur, K. (K.), Clahsen-van Groningen, M.C, van den Bosch, T.P.P. (T. P.P.), de Graav, G.N, Hesselink, D.A, Samsom, J.N, … Boer, K. (2018). Characterization of ectopic lymphoid structures in different types of acute renal allograft rejection. Clinical and Experimental Immunology. doi:10.1111/cei.13099