Natural regulatory plasma cells

B cells can generate several types of antibody-secreting cells, including plasmablasts that divide and are short lived, as well as plasma cells that do not proliferate and can persist for extended time periods. Here, we discuss the identification of a novel subset of non-dividing plasma cells specialized in the production of interleukin(IL)-10. These cells develop at steady state, including in germ-free mice, via a mechanism dependent on the B cell receptor for antigen and possibly involving the recognition of damaged cells. They are characterized by the expression of the inhibitory receptor LAG-3, and also express CD200, PD-L1, as well as PD-L2. Their specialized epigenome allows them to produce IL-10 within hours after stimulation, which altogether qualify these cells as natural regulatory plasma cells.