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

: Steines, L.; Poth, H.; Schuster, A.; Geissler, E.K.; Amann, K.; Banas, B.; Bergler, T.


Transplantation 104 (2020), No.1, pp.e16-e22
ISSN: 0041-1337
ISSN: 1534-6080
Journal Article
Fraunhofer ITEM ()

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 evaluate d 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.