PD-L1 Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment.

B cells play an important role in the development and maintenance of rheumatoid arthritis (RA). Although IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) able to suppress autoimmune and inflammatory responses, recent reports showed that B cell-mediated immune suppression may also occur independent of IL-10. For instance, B cells can modulate T cell immune responses through the expression of regulatory molecules such as PD-L1. So far, PD-L1-expressing B cells have not been analyzed in RA patients. To analyze the frequency of PD-L1-expressing B cells in the peripheral blood of RA patients compared to healthy controls (HC) matched for sex and age, their function on T cell response and their changes in response to therapy. Fresh peripheral blood B cells from RA patients and HC were characterized by flow cytometry and their functionality assessed in a co-culture system with autologous T cells. The frequencies of CD19PD-L1 B cells, CD24CD38PD-L1 and CD24CD38PD-L1 B cells were significantly lower in untreated RA patients than in HC. In a follow-up study, the frequencies of PD-L1 B cells (CD19PD-L1 B cells, CD24CD38PD-L1 and CD24CD38PD-L1 B cells) increased significantly after treatment in good responder patients, although the frequency of total CD24CD38 B cells decreased. CD19 B cells from untreated RA patients and HC upregulated PD-L1 expression similarly upon stimulation with CpG plus IL-2 and were able to suppress, , CD8 T cell proliferation and cytokine production in a PD-L1-dependent manner. Our results show that PD-L1 B cells exhibiting T cell suppressive capacity are significantly decreased in untreated RA patients but increase in response to successful treatment. PD-L1 expression on B cells from RA patients can be modulated and PD-L1 B cells could thus provide new perspectives for future treatment strategies.