Emerging roles of checkpoint molecules on B cells

Immune checkpoint molecules, including both co-inhibitory molecules and co-stimulatory molecules, are known to play critical roles in regulating T-cell responses. During the last decades, immunotherapies targeting these molecules (such as programmed cell death 1 (PD-1), and lymphocyte activation gene 3 (LAG-3)) have provided clinical benefits in many cancers. It is becoming apparent that not only T cells, but also B cells have a capacity to express some checkpoint molecules. These were originally thought to be only the markers for regulatory B cells which produce IL-10, but recent studies suggest that these molecules (especially T-cell immunoglobulin and mucin domain 1 (TIM-1), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and PD-1) can regulate intrinsic B-cell activation and functions. Here, we focus on these molecules and summarize their characteristics, ligands, and functions on B cells.