PD-L1+ REGULATORY B CELLS ARE SIGNIFICANT DECREASED IN RHEUMATOID ARTHRITIS PATIENS AND INCREASE AFTER GOOD TREATMENT RESPONSE

Cancun

Congreso; ALAI; 2018

Background: It has been demonstrated that 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) studied that suppress autoimmune and inflammatory responses, recent reports have also shown that immune suppression independent of IL-10 also occurs. For instance, it has been reported that B cells can modulate T cell immune responses through the expression of regulatory molecules such as PD-L1, however PD-L1-expressing B cells have not been analyzed in RA patients.Objective: To analyze the frequency of PD-L1-expressing B cells in peripheral blood of RA patients compared to matched-healthy controls (HC), their function on T cell response and their changes in response to therapy.Methods: Fresh peripheral blood B cells from 69 RA patients and 25 HC were characterized by flow cytometry and their functionality was assessed in a co-culture system with autologous T cells.Results: The frequencies of CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells were significantly decreased in untreated RA patients compared to HC (p<0.01). In a follow-up study, the frequencies of PD-L1+ B cells (CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells) were significantly increased after treatment in good responder patients (p<0.01), although the frequency of total CD24hiCD38hi B cells decreased (p<0.01). CD19+ B cells from untreated RA patients and HC were equally able to up-regulate PD-L1 expression 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 (p<0.05).Conclusions: Our results show that T cell suppressive-PD-L1+ B cells are significantly decreased in untreated RA patients but increases in response to successful treatment. PD-L1 expression on B cells from RA patients can be in vitro modulated and thereby, PD-L1+ B cells could provide new perspectives for future treatment strategies.