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Steines, Louisa ; Poth, Helen ; Herrmann, Marlene ; Schuster, Antonia ; Banas, Bernhard ; Bergler, Tobias

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

Steines, Louisa , Poth, Helen, Herrmann, Marlene, Schuster, Antonia, 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), p. 8045.

Date of publication of this fulltext: 13 Jan 2021 14:40
Article
DOI to cite this document: 10.5283/epub.44209


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 ...

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.



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Details

Item typeArticle
Journal or Publication TitleInternational Journal of Molecular Sciences
Publisher:MDPI
Open Access Type:Gold (with APC)
Place of Publication:BASEL
Volume:21
Number of Issue or Book Chapter:21
Page Range:p. 8045
Date28 October 2020
InstitutionsMedicine > Abteilung für Nephrologie
Identification Number
ValueType
10.3390/ijms21218045DOI
KeywordsRICH ACUTE REJECTION; ALLOGRAFT-REJECTION; GERMINAL CENTER; INFLAMMATION; EXPRESSION; SURVIVAL; DIFFERENTIATION; NEOGENESIS; CHEMOKINES; FIBROSIS; tertiary lymphoid organs; kidney transplantation; B cells; BAFF
Dewey Decimal Classification600 Technology > 610 Medical sciences Medicine
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgYes
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-442094
Item ID44209

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