Enhanced Programmed Death 1 and Diminished Programmed Death Ligand 1 Up-Regulation Capacity of Post-Activated Lupus B Cells.

Abstract

To assess the expression of programmed death 1 (PD-1), PD ligand 1 (PD-L1), and PD-L2 by B cells from patients with systemic lupus erythematosus (SLE) at baseline and after in vitro stimulation and to analyze their functional relationship to B cell proliferation. Peripheral blood mononuclear cells obtained from 29 SLE patients and 27 healthy donors were stimulated with interleukin-2 (IL-2)/IL-10, anti-B cell receptor (anti-BCR), CpG, and CD40L alone or in combination. Expression of PD-1, PD-L1, and PD-L2 on defined B cell subsets as well as on CD3+ T cells was analyzed by flow cytometry at baseline and after 48 hours of stimulation. Additionally, after 48 hours of stimulation, CD71 was evaluated as a proliferation marker on CD19+CD20+ B cells. Increased PD-1 expression was characteristic of unstimulated lupus B cells and T cells. Upon stimulation of B cells with IL-2/IL-10, anti-BCR, CpG, and CD40L for 48 hours, the capacity of SLE B cells to up-regulate PD-L1 expression was substantially diminished (P = 0.0006) along with reduced B cell proliferation (P = 0.0039). Reduced PD-L1 expression was inversely correlated with the presence of the interferon signature (r = -0.8571, P < 0.0001) and the clinical SLE Disease Activity Index score (r = -0.5696, P = 0.0087). Post-activated, hyporesponsive lupus B cells are characterized by a phenotype of increased PD-1, functionally diminished PD-L1 up-regulation capacity, and reduced proliferation upon stimulation.