Presence of intragraft B cells during acute renal allograft rejection is accompanied by changes in peripheral blood B cell subsets

• DOI: 10.1111/cei.13269
• Publication Date: 2019-02-03T11:08:28Z
• Authors: S Heidt; M Vergunst; J D H Anholts; G M J S Swings; E M J Gielis; K E Groeneweg; M J Witkamp; J W de Fijter; M E J Reinders; D L Roelen; M Eikmans; F H J Claas
• Keywords: Adult; Graft Rejection; Male; memory B cell; T-Lymphocytes; Kidney; B cell infiltration; 03 medical and health sciences; 0302 clinical medicine; Cell Movement; Isoantibodies; Humans; Aged; B-Lymphocytes; flow cytometry; Graft Survival; T cell; Original Articles; Middle Aged; Antigens, CD20; Chemokine CXCL13; Kidney Transplantation; Lymphocyte Subsets; 3. Good health; Acute Disease; Blood Circulation; B cell interaction; Female; Immunologic Memory

Summary B cells have various functions, besides being plasma cell precursors. We determined the presence of intragraft B cells at time of acute rejection (AR) and looked for correlates of B cell involvement in peripheral blood. Renal biopsies at time of AR or stable graft function were analysed for the presence of B cells and B cell-related gene expression, as well as C4d staining. Peripheral blood B cell subset distribution was analysed at various time-points in patients with AR and controls, alongside serum human leucocyte antigen (HLA) antibodies. AR was accompanied by intragraft CD20+ B cells, as well as elevated CD20 (MS4A1) and CD19 gene expression compared to controls. B cell infiltrates were proportional to T cells, and accompanied by the chemokine pair C-X-C motif chemokine ligand 13 (CXCL13)–C-X-C motif chemokine receptor 5 (CXCR5) and B cell activating factor (BAFF). Peripheral blood memory B cells were decreased and naive B cells increased at AR, in contrast to controls. While 22% of patients with AR and 5% of controls showed de-novo donor-specific antibodies (DSA), all biopsies were C4d-negative. These results suggest a role for B cells in AR by infiltrating the graft alongside T cells. We hypothesize that the shift in peripheral blood B cell composition is related to the graft infiltration at time of AR.