Regulatory and transitional B cells: potential biomarkers and therapeutic targets in organ transplantation.

Abstract

Regulatory B cells (Bregs) play a prominent role in various disease settings. While progress has been hindered by the lack of a specific Breg marker, new findings highlight their role modulating the alloimmune response and promoting allograft survival. Herein, we focus on the recent advances in Breg biology and their role in transplantation. We review studies showing that T-cell immunoglobulin and mucin domain 1 (TIM-1) is an inclusive and functional Breg marker in mice that may have human relevance. We highlight the utility of the B cell interleukin-10/tumor necrosis factor-alpha (IL-10/TNFα) ratio in identifying underlying immunological reactivity and predicting clinical outcomes in kidney transplantation. This may identify patients requiring more immunosuppression and provide insight into potential therapeutic approaches that can modulate the Breg: B effector cell (Beff) balance. Emerging data support Bregs as potent modulators of immune responses in humans. Their ability to promote allograft survival must await development of approaches to expand Bregs in vitro/in vivo . The low IL-10/TNFα ratio reflecting decreased Breg/Beff balance, predicts acute rejection (AR) and poorer outcomes in renal transplantation. It remains to be determined whether this paradigm can be extended to other allografts and whether therapy aiming to correct the relative deficiency of Bregs will improve outcomes.