PD-L1⁺ Regulatory B Cells from Rheumatoid Arthritis Patients Have Impaired Function in Suppressing IFN-ү and IL-21...

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease. The pathomechanism of RA depends on both B and T cells. Regulatory B cells (Breg) have been shown to suppress T-cell immune responses and play a key role in modulating autoimmune processes. We aimed to investigate the possibility of utilizing PD-L1⁺ Breg cells in downregulating the Th cells' immune response in healthy individuals and RA patients. We hypothesized that the PD-1/PD-1L interaction plays a key role in this process, which may be defective in autoimmune diseases. We separated T and B cells from the peripheral blood of healthy volunteers and RA patients by magnetic cell sorting, and Th cells and Treg cells were isolated by fluorescence-activated cell sorting. The cytokine production by CD4⁺ Th cells was detected by intracellular flow cytometry. CpG and CD40L stimulations were applied to induce PD-L1^hi expressing Breg cells. We found that the frequency of PD-L1^hi cells is significantly lower in all B-cell subsets in RA compared to healthy controls. Functional analysis of induced PD-L1⁺ Breg cells in coculture with activated autologous Th cells has shown that healthy control samples containing higher levels of PD-L1^hi Breg cells significantly inhibit IFN-ү and IL-21 production by Th cells. In contrast, RA patients' samples with lower levels of PD-L1^hi Breg cells failed to do so. Since the expression of PD-L1 on B cells can be modulated in vitro to induce Breg cell suppressive capacity, these data may provide new perspectives for future therapy for RA.