Journal Article

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

Ferrero, Paola V., Gruppi, Adriana, Cadile, Isaac I., Stancich, Maria I., Taboada Bonfanti, Maria C., Mussano, Eduardo, Zacca, Estefanía R., Onetti, Laura, Ramello, María C., Montes, Carolina L., Onofrio, Luisina I., Acosta Rodríguez, Eva V., Acosta, Cristina D. V., Alonso, Sergio M.

2018

Overview

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 CD19 PD-L1 B cells, CD24 CD38 PD-L1 and CD24 CD38 PD-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 (CD19 PD-L1 B cells, CD24 CD38 PD-L1 and CD24 CD38 PD-L1 B cells) increased significantly after treatment in good responder patients, although the frequency of total CD24 CD38 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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Antibodies / bregs / C-reactive protein / CD19 antigen / CD8 antigen / Cell culture / Cell proliferation / Cytokines / Disease / Flow cytometry / Immune response / Immune response (cell-mediated) / Immunology / Inflammation / Interleukin 10 / Lymphocytes / Lymphocytes B / Lymphocytes T / Patients / PD-L1 / PD-L1 protein / Peripheral blood / rheumatic diseases / Rheumatoid arthritis / Rheumatology / Stem cells / TNF inhibitors