Anti-BAFF Treatment Interferes With Humoral Responses in a Model of Renal Transplantation in Rats.
Allografts
/ cytology
Animals
Antibodies, Monoclonal
/ administration & dosage
B-Cell Activating Factor
/ antagonists & inhibitors
B-Lymphocytes
/ immunology
Disease Models, Animal
Graft Rejection
/ immunology
Injections, Intraperitoneal
Isoantigens
/ immunology
Kidney
/ cytology
Kidney Failure, Chronic
/ surgery
Kidney Transplantation
/ adverse effects
Male
Rats
Rats, Inbred BN
Rats, Inbred Lew
Spleen
/ cytology
Transplantation, Homologous
/ adverse effects
Journal
Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
pubmed:
15
10
2019
medline:
2
10
2020
entrez:
15
10
2019
Statut:
ppublish
Résumé
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. 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. 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. Anti-BAFF treatment interferes with humoral responses at multiple levels in this model of allogeneic RTx.
Sections du résumé
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.
Identifiants
pubmed: 31609901
doi: 10.1097/TP.0000000000002992
pii: 00007890-202001000-00017
doi:
Substances chimiques
Antibodies, Monoclonal
0
B-Cell Activating Factor
0
Isoantigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16-e22Commentaires et corrections
Type : CommentIn
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