Plasmablasts induced by chitosan oligosaccharide secrete natural IgM to enhance the humoral immunity in grass carp

Chitosan oligosaccharide (COS) is an attractive immunopotentiator capable of driving humoral immunity in vertebrates, but its cellular and molecular mechanisms still require elucidation. In this study, COS induced the proliferation and differentiation of splenic IgM+ B cells into IgMlo and IgMhi B cell subsets in grass carp (Ctenopharyngodon idella). The IgMlo B cells were further identified as short-lived plasmablasts that secreted natural IgM with binding-abilities to lipopolysaccharide (LPS) and peptidoglycan (PGN). Moreover, the mannose receptor (MR) and integrins were discovered and identified as the binding-receptors of COS on IgMlo plasmablasts. The MR synergized with integrins to trigger intracellular signal transduction to boost plasmablast generation and expansion. Notably, IgMlo plasmablasts originally generated in spleen but they migrated into blood to secrete natural IgM, which augmented the serum bactericidal activity. Taken together, this study revealed the cellular and molecular mechanisms of COS-triggered humoral immunity in fish.