AN EVOLUTIONARILY ANCIENT INNATE IMMUNE ROLE IDENTIFIED IN PLASMA CELLS
Oriol Sunyer, University of Pennsylvania
Jacob Paiano1, Fumio Takizawa1, Yasuhiro Shibasaki1, Joel Wilmore2, David Allman2, J. Oriol
1. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104
2. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104
Antibodies are the crown jewel of humoral adaptive immune responses and, plasma cells (PCs) are by far the most specialized and main antibody-secreting cells. Until very recently, PCs were viewed exclusively as antibody-producing factories. However, this perception is starting to shift as immunomodulatory roles for PCs have recently been identified. In line with that changing scenario, here we show for the first time that terminally differentiated murine PCs efficiently perform phagocytosis, a function regarded as a crucial mechanism of innate immunity. More specifically, we show that a large subset of splenic PCs in mice have a strikingly high phagocytic capacity. We also show that phagocytic plasma cells (PhPCs) could phagocytose E. coli and latex beads, and that by transmission electron microscopy, sorted PhPCs have the typical morphology of a PC, which is characterized by abundant rough endoplasmatic reticulum (RER) in the cytoplasm. Critically, upon LPS injection into the mouse peritoneal cavity, we observed a ~16 fold increase in the number of PhPCs, which represented ~1% of the total splenocytes. This dramatic increase in the number of PhPCs three days after LPS injection strongly suggests a role for PhPCs early in infection. This role appears to be evolutionarily conserved as similar cells were detected in rainbow trout, a teleost fish. Overall, here we provide the first demonstration that PCs, the most central component of adaptive immunity, also play a key evolutionarily ancient innate immune role, and thus, our discovery represents a paradigm shift in our understanding of PCs function.