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Abnormal Distribution of B-Cell Populations Associated with Impaired Regulatory Functions in Chronic Antibody Mediated Rejection

A. Nouël, I. Segalen, A. Grall, J. Pers, S. Hillion, Y. Le Meur

EA2216 Immunology and Pathology, University of Brest, Brest, France
Nephrology, CHRU Cavale Blanche, Brest, France

Meeting: 2013 American Transplant Congress

Abstract number: D1455

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.

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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 June 6, 2025.

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