The Origin And Impact Of Polyamine Burst In B Cell Activation

Via emerging novel mass spectrometry technology,we found that polyamines and its derivative,exhibit a rapid and transient burst in the early stage of B cell activation.Polyamines shown no significant feedback on the phosphorylation of early signaling molecules,the temporal and spatial dynamics of PIP2,and the formation of immune synapses during B cell activation,but inhibited calcium flux signaling and early ROS,suggesting that polyamines may be part of the "brake" mechanism of B cell activation.As long-term activation-related events,polyamines may protective B cells from activation-induced cell death,and boost humoral immunity level in vivo.By investigating the upstream of the polyamines burst through various means of cell biology,we found the subcellular distribution of the rate-limiting enzyme of polyamine synthesis,ornithine decarboxylase,modified in the activation of B cell.Cytoskeleton remodeling induced by B cell activation may inhibit C-terminal degron activity of ODC,which leads to ODC accumulating in cytosol then the polyamine burst.Focusing on the short-term effect of polyamines manipulation,as downstream of the polyamines burst,we found that polyamines broadly upregulate the expression of pro-inflammatory factors in B cells and epithelial cells.This rapid process may be independent on TFEB.Through demostration of the BACH2-BCL6 balance models,polyamines shown function of signal amplification in B cells.In summary,polyamines have two sides in the early activation stage: on the one hand,they can act as a self-limiting signal to prevent the overactivation of B cells;on the other hand,they can amplify the signaling in B cells during activation by enhancing the translation level.By answering the key scientific question "how polyamines participate in the activation-related events in the early stage of B cell activation",this study revealed details of polyamines dynamics in the early stage of lymphocyte activation,and introduced it as a novel second messenger into lymphocyte signal.This work will further supplement the understanding of the function of polyamines in the fields of cell biology,immunology and nutrition research.