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

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

*Corresponding author for this work

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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.

Original languageEnglish
Pages (from-to)403-414
Number of pages12
JournalClinical and Experimental Immunology
Volume196
Issue number3
DOIs
Publication statusPublished - Jun 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 The Authors Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology

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