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

Objective 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. Methods 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 CD 40L alone or in combination. Expression of PD ‐1, PD ‐L1, and PD ‐L2 on defined B cell subsets as well as on CD 3+ T cells was analyzed by flow cytometry at baseline and after 48 hours of stimulation. Additionally, after 48 hours of stimulation, CD 71 was evaluated as a proliferation marker on CD 19+ CD 20+ B cells. Results 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 CD 40L 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). Conclusion 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.