An Ancient BCR-like Signaling Promotes ICP Production and Hemocyte Phagocytosis in Oyster

BCR/TCR-based adaptive immune systems arise in the jawed vertebrates, and B cell receptors (BCRs) play an important role in the clonal selection of B cells and their differentiation into antibody-secreting plasma cells. The existence of BCR-like molecule and the activation mechanism of the downstream response are still not clear in invertebrates. In this study, an ancient BCR-like molecule (designated as CgIgR) with an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic tail was identified from the Pacific oyster Crassostrea gigas to investigate its involvement in immune response. CgIgR could bind different bacteria through five extracellular Ig domains and formed dimers. The activated CgIgR recruited CgSyk to promote CgERK phosphorylation. The CgIgR-mediated signaling promoted the production of immunoglobulin domain-containing proteins (CgICP-2 and CgLRRIG-1) through inducing CgH3K4me2. The produced CgICPs eventually facilitated hemocytes to phagocytize and eliminate V. splendidus. This study proposed that there was an ancient BCR-like molecule and BCR-like signaling in molluscs.