miR-148a weaves its thread into the plasma cell fate.

The plasma cells (PC) are characterized by their rarity, their formidable capacity to continuously secrete massive amounts of antibodies and the potential to live through the whole life span of the organism that houses them. Because of the potency of their effector function, their differentiation and survival are tightly regulated. The PC identity is implemented and maintained by a transcriptional program that allow them to face the challenges entailed by their longevity and high metabolic activity. The main transcription factors overseeing this transcriptional network have been identified (BLIMP1, IRF4, XBP1), but new players, like miRNA, continue to emerge and bring new layers of complexity to the regulatory loops. In the current issue of the European Journal of Immunology [Eur. J. Immunol. 2021. 51: 1089-1109], Pracht et al. identify miR-148a as a significant actor of the PC program that favors the differentiation through the inhibition of competitor fates, and supports the survival and fitness of the long-lived PC. In this commentary, we will discuss the place of miR-148a in the PC transcriptional network and its potential as a therapeutic target in PC-driven diseases.