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Presence of intragraft B cells during acute renal allograft rejection is accompanied by changes in peripheral blood B cell subsets
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
Affiliation:1. Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands;2. Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, the Netherlands
Abstract: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.
Keywords:B cell infiltration  flow cytometry  memory B cell  T cell/B cell interaction
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