B-cell Deficiency Attenuates Transplant Glomerulopathy in a Rat Model of Chronic Active Antibody-mediated Rejection

• Published in: Transplantation Vol. 105; no. 7; p. 1516
• Main Authors: Reese, Shannon R, Wilson, Nancy A, Huang, Yabing, Ptak, Lucille, Degner, Kenna R, Xiang, Ding, Redfield, Robert R, Zhong, Weixiong, Panzer, Sarah E
• Format: Journal Article
• Language: English
• Published: United States 01.07.2021
• Subjects: Animals; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Cell Proliferation; Cells, Cultured; Chronic Disease; Coculture Techniques; Cytokines - genetics; Cytokines - metabolism; Disease Models, Animal; Glomerulonephritis - genetics; Glomerulonephritis - immunology; Glomerulonephritis - metabolism; Glomerulonephritis - prevention & control; Graft Rejection - genetics; Graft Rejection - immunology; Graft Rejection - metabolism; Graft Rejection - prevention & control; Immunity, Cellular; Immunity, Innate; Inflammation Mediators - metabolism; Isoantibodies - blood; Kidney - immunology; Kidney - metabolism; Kidney - pathology; Lymphocyte Activation; Rats; Rats, Inbred F344; Rats, Inbred Lew; Rats, Transgenic; Spleen - immunology; Spleen - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 1534-6080
• DOI: 10.1097/TP.0000000000003530

Transplant glomerulopathy (TG) is a pathological feature of chronic active antibody-mediated rejection (cAMR) and is associated with renal allograft failure. The specific role of B cells in the pathogenesis of TG is unclear. We used a minor mismatched rat kidney transplant model with B cell-deficient recipients, generated by clustered regularly interspaced short palindromic repeats/Cas9 technology, to investigate the impact of B-cell depletion on the pathogenesis of TG. We hypothesized that B-cell deficiency would prevent TG in the rat kidney transplant model of cAMR. Treatment groups included syngeneic, allogeneic, sensitized allogeneic, and B cell-deficient allogeneic transplant recipients. B cell-deficient recipients demonstrated reduced TG lesions, decreased microvascular inflammation, reduced allograft infiltrating macrophages, and reduced interferon gamma transcripts within the allograft. Allograft transcript levels of interferon gamma, monocyte chemoattractant protein-1, and interleukin-1β correlated with numbers of intragraft macrophages. B cell-deficient recipients lacked circulating donor-specific antibodies and had an increased splenic regulatory T-cell population. In this model of cAMR, B-cell depletion attenuated the development of TG with effects on T cell and innate immunity.