Anti-BAFF Treatment Interferes With Humoral Responses in a Model of Renal Transplantation in Rats

Steines, Louisa and Poth, Helen and Schuster, Antonia and Geissler, Edward K. and Amann, Kerstin and Banas, Bernhard and Bergler, Tobias (2020) Anti-BAFF Treatment Interferes With Humoral Responses in a Model of Renal Transplantation in Rats. TRANSPLANTATION, 104 (1). E16-E22. ISSN 0041-1337, 1534-6080

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Abstract

Background. B-cell-activating factor (BAFF) is associated with donor-specific antibodies (DSA) and poorer outcomes after renal transplantation (RTx). We examined the effects of anti-BAFF treatment on B cells, expression of costimulatory molecules and cytokines, germinal centers (GCs), and DSA formation in an RTx model in rats. Methods. Anti-BAFF antibody was injected on days 3, 17, 31, and 45 after allogeneic RTx. Rats received reduced dose cyclosporine A for 28 or 56 days to allow chronic rejection and DSA formation. Leukocytes, B-cell subsets, and DSA were measured using flow cytometry; expression of cytokines and costimulatory molecules was measured by quantitative polymerase chain reaction, and GCs and T follicular helper were assessed using immunohistochemistry. Rejection was evaluated by a nephropathologist. Results. Anti-BAFF treatment reduced the frequency of B cells in allografts and spleen. Naive B cells were strongly reduced by anti-BAFF treatment in all compartments. Messenger RNA expression of interleukin-6 and the costimulatory molecules CD40 and inducible T cell costimulator ligand was significantly reduced in anti-BAFF-treated rats. GC area was smaller and plasmablasts/plasma cell numbers lower in anti-BAFF-treated rats, which was reflected by less DSA in certain IgG subclasses. Conclusions. Anti-BAFF treatment interferes with humoral responses at multiple levels in this model of allogeneic RTx.

Item Type: Article
Uncontrolled Keywords: FOLLICULAR HELPER-CELLS; MEDIATED REJECTION; B-CELLS; KIDNEY-TRANSPLANTATION; EXPRESSION; SURVIVAL;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Medicine > Abteilung für Nephrologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 07 Apr 2021 08:28
Last Modified: 07 Apr 2021 08:28
URI: https://pred.uni-regensburg.de/id/eprint/45481

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