B Cell Activating Factor (BAFF) Is Required for the Development of Intra-Renal Tertiary Lymphoid Organs in Experimental Kidney Transplantation in Rats

Steines, Louisa and Poth, Helen and Herrmann, Marlene and Schuster, Antonia and Banas, Bernhard and Bergler, Tobias (2020) B Cell Activating Factor (BAFF) Is Required for the Development of Intra-Renal Tertiary Lymphoid Organs in Experimental Kidney Transplantation in Rats. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (21): 8045. ISSN , 1422-0067

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Abstract

Intra-renal tertiary lymphoid organs (TLOs) are associated with worsened outcome in kidney transplantation (Ktx). We used an anti-BAFF (B cell activating factor) intervention to investigate whether BAFF is required for TLO formation in a full MHC-mismatch Ktx model in rats. Rats received either therapeutic immunosuppression (no rejection, NR) or subtherapeutic immunosuppression (chronic rejection, CR) and were sacrificed on d56. One group additionally received an anti-BAFF antibody (CR + AB). Intra-renal T (CD3(+)) and B (CD20(+)) cells, their proliferation (Ki67(+)), and IgG(+) plasma cells were analyzed by immunofluorescence microscopy. Formation of T and B cell zones and TLOs was assessed. Intra-renal expression of TLO-promoting factors, molecules of T:B crosstalk, and B cell differentiation was analyzed by qPCR. Intra-renal B and T cell zones and TLOs were detected in CR and were associated with elevated intra-renal mRNA expression of TLO-promoting factors, including CXCL13, CCL19, lymphotoxin-beta, and BAFF. Intra-renal plasma cells were also elevated in CR. Anti-BAFF treatment significantly decreased intra-renal B cell zones and TLO, as well as intra-renal B cell-derived TLO-promoting factors and B cell differentiation markers. We conclude that BAFF-dependent intra-renal B cells promote TLO formation and advance local adaptive alloimmune responses in chronic rejection.

Item Type: Article
Uncontrolled Keywords: RICH ACUTE REJECTION; ALLOGRAFT-REJECTION; GERMINAL CENTER; INFLAMMATION; EXPRESSION; SURVIVAL; DIFFERENTIATION; NEOGENESIS; CHEMOKINES; FIBROSIS; tertiary lymphoid organs; kidney transplantation; B cells; BAFF
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Abteilung für Nephrologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 08 Mar 2021 10:33
Last Modified: 08 Mar 2021 10:33
URI: https://pred.uni-regensburg.de/id/eprint/43475

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