Chronic antibody (Ab) mediated rejection (cAMR) represents the major problem in renal transplantation. The aim of our study was to analyze B lymphocyte (LB) distribution and function in the cAMR.
LB phenotype was determined by flow cytometry in 18 stable patients (ST) (no rejection, no DSA and a one year biopsy without allograft glomerulopathy or rejection), 17 patients with cAMR (positive DSA, allograft glomerulopathy and/or C4d staining) and 35 controls (C) (blood donors). The distribution of mature blood LB (Bm1 to Bm5) and memory LB was analyzed using IgD/CD38/CD19/CD27 labeling, transitional (Tr) and CD5 LB using CD19/CD24/CD38/CD5.
LB functions were analyzed using mixed autologous lymphocyte reaction with activated T lymphocyte (LT). Proliferation and Th1 cytokine secretion of isolated CFSE labeled LT in the presence of LB were compared between the 3 groups. Suppressive cytokines such as TGFΒ and IL-10 and the regulatory enzyme IDO were also assessed by ELISA.
We evidenced a decrease of the ratio activated LB/memory LB (Bm2+Bm2'/eBm5+Bm5) in the cAMR compared to ST and C (2.1 ± 0.4 vs 5.7±1, P=0,002 and vs 3.4±0,3, P=0,02, respectively). We also demonstrated an increase in post switched memory LB (IgD–CD27+) with upregulated presenting cell capacity in cAMR compared to ST (25.4±4.1 cells /¯o;L vs 10±1.3, P=0,002). Additionally, Tr LB (CD19+CD24highCD38high) were decreased in cAMR compared to ST (2.5%± 0.4 vs 9.4±1.4%, P< 0.0001). This abnormal LB distribution is strongly correlated with autoimmune manifestations as demonstrated by nuclear autoAb detection (P=0,015).We also found that LB from cAMR display an impaired regulatory function on LT proliferation (3.7% of inhibition of LT proliferation versus 39 % in ST) and Th1 differentiation (preserved TNFΑ and INFΓ production that was decreased in ST). We have additionally shown that LB from cAMR present a lack of TGFΒ and IL-10 production in co-culture associated with an significantly decrease of IDO production leading to a defect in the capacity of activated-LB to induce regulatory LT and to control LT response.
Patients with cAMR display a unique LB phenotype and functional abnormalities as evidenced by the loss of LB suppressive activity. This LB signature has the potential to be used as a cellular biomarker for specific deficit in patients and might guide therapy in transplantation.
To cite this abstract in AMA style:Nouël A, Segalen I, Grall A, Pers J, Hillion S, Meur YLe. Abnormal Distribution of B-Cell Populations Associated with Impaired Regulatory Functions in Chronic Antibody Mediated Rejection [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/abnormal-distribution-of-b-cell-populations-associated-with-impaired-regulatory-functions-in-chronic-antibody-mediated-rejection/. Accessed October 27, 2020.
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